[House Hearing, 109 Congress]
[From the U.S. Government Publishing Office]
THE THREAT OF AND PLANNING FOR PANDEMIC FLU
=======================================================================
HEARING
before the
SUBCOMMITTEE ON HEALTH
of the
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED NINTH CONGRESS
FIRST SESSION
__________
MAY 26, 2005
__________
Serial No. 109-21
__________
Printed for the use of the Committee on Energy and Commerce
Available via the World Wide Web: http://www.access.gpo.gov/congress/
house
__________
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COMMITTEE ON ENERGY AND COMMERCE
JOE BARTON, Texas, Chairman
RALPH M. HALL, Texas JOHN D. DINGELL, Michigan
MICHAEL BILIRAKIS, Florida Ranking Member
Vice Chairman HENRY A. WAXMAN, California
FRED UPTON, Michigan EDWARD J. MARKEY, Massachusetts
CLIFF STEARNS, Florida RICK BOUCHER, Virginia
PAUL E. GILLMOR, Ohio EDOLPHUS TOWNS, New York
NATHAN DEAL, Georgia FRANK PALLONE, Jr., New Jersey
ED WHITFIELD, Kentucky SHERROD BROWN, Ohio
CHARLIE NORWOOD, Georgia BART GORDON, Tennessee
BARBARA CUBIN, Wyoming BOBBY L. RUSH, Illinois
JOHN SHIMKUS, Illinois ANNA G. ESHOO, California
HEATHER WILSON, New Mexico BART STUPAK, Michigan
JOHN B. SHADEGG, Arizona ELIOT L. ENGEL, New York
CHARLES W. ``CHIP'' PICKERING, ALBERT R. WYNN, Maryland
Mississippi, Vice Chairman GENE GREEN, Texas
VITO FOSSELLA, New York TED STRICKLAND, Ohio
ROY BLUNT, Missouri DIANA DeGETTE, Colorado
STEVE BUYER, Indiana LOIS CAPPS, California
GEORGE RADANOVICH, California MIKE DOYLE, Pennsylvania
CHARLES F. BASS, New Hampshire TOM ALLEN, Maine
JOSEPH R. PITTS, Pennsylvania JIM DAVIS, Florida
MARY BONO, California JAN SCHAKOWSKY, Illinois
GREG WALDEN, Oregon HILDA L. SOLIS, California
LEE TERRY, Nebraska CHARLES A. GONZALEZ, Texas
MIKE FERGUSON, New Jersey JAY INSLEE, Washington
MIKE ROGERS, Michigan TAMMY BALDWIN, Wisconsin
C.L. ``BUTCH'' OTTER, Idaho MIKE ROSS, Arkansas
SUE MYRICK, North Carolina
JOHN SULLIVAN, Oklahoma
TIM MURPHY, Pennsylvania
MICHAEL C. BURGESS, Texas
MARSHA BLACKBURN, Tennessee
Bud Albright, Staff Director
David Cavicke, Deputy Staff Director and General Counsel
Reid P.F. Stuntz, Minority Staff Director and Chief Counsel
______
Subcommittee on Health
NATHAN DEAL, Georgia, Chairman
RALPH M. HALL, Texas SHERROD BROWN, Ohio
MICHAEL BILIRAKIS, Florida Ranking Member
FRED UPTON, Michigan HENRY A. WAXMAN, California
PAUL E. GILLMOR, Ohio EDOLPHUS TOWNS, New York
CHARLIE NORWOOD, Georgia FRANK PALLONE, Jr., New Jersey
BARBARA CUBIN, Wyoming BART GORDON, Tennessee
JOHN SHIMKUS, Illinois BOBBY L. RUSH, Illinois
JOHN B. SHADEGG, Arizona ANNA G. ESHOO, California
CHARLES W. ``CHIP'' PICKERING, GENE GREEN, Texas
Mississippi TED STRICKLAND, Ohio
STEVE BUYER, Indiana DIANA DeGETTE, Colorado
JOSEPH R. PITTS, Pennsylvania LOIS CAPPS, California
MARY BONO, California TOM ALLEN, Maine
MIKE FERGUSON, New Jersey JIM DAVIS, Florida
MIKE ROGERS, Michigan TAMMY BALDWIN, Wisconsin
SUE MYRICK, North Carolina JOHN D. DINGELL, Michigan,
MICHAEL C. BURGESS, Texas (Ex Officio)
JOE BARTON, Texas,
(Ex Officio)
(ii)
C O N T E N T S
__________
Page
Testimony of:
Crosse, Marcia, Director, Health Care Issues, United States
G.overnment Accountability Office.......................... 47
Fauci, Anthony S., Director, National Institute of Allergy
and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services.................... 21
Gellin, Bruce G., Director, National Vaccine Program Office,
Department of Health and Human Services.................... 26
Gerberding, Julie L., Director, Centers for Disease Control
and Prevention, Department of Health and Human Services.... 15
Hosbach, Phillip, Vice President, Immunization Policy and
Government Relations, sanofi-pasteur....................... 65
Iacuzio, Dominick A., Medical Director, Hoffmann-La Roche.... 70
Pavia, Andrew T., Chairman, Taskforce on Pandemic Influenza,
Infectious Diseases Society of America, and Professor and
Chief, Division of Pediatric Infectious Diseases,
University of Utah Medical Center.......................... 59
Tripp, Ralph A., Chairman, Georgia Research Alliance, and
Professor, Department of Infectious Diseases, University of
Georgia, College of Veterinary Medicine.................... 75
(iii)
THE THREAT OF AND PLANNING FOR PANDEMIC FLU
----------
THURSDAY, MAY 26, 2005
House of Representatives,
Committee on Energy and Commerce,
Subcommittee on Health,
Washington, DC.
The subcommittee met, pursuant to notice, at 10:05 a.m., in
room 2123 of the Rayburn House Office Building, Hon. Nathan
Deal (chairman) presiding.
Members present: Representatives Deal, Hall, Shadegg,
Pitts, Bono, Ferguson, Burgess, Barton (ex officio), Brown,
Waxman, Eshoo, Green, DeGette, Allen, and Baldwin.
Staff present: Chuck Clapton, chief health counsel; Ryan
Long, professional staff; Nandan Kenkermath, majority counsel;
Eugenia Edwards, legislative clerk; Brandon Clark, health
policy coordinator; John Ford, minority counsel; and Jessica
McNiece, research assistant.
Mr. Deal. Call to order. Please close the doors in the back
and we will get started. The Chair recognizes himself for an
opening statement.
I certainly want to welcome everyone to this hearing today
and our distinguished panel members. We have two panels that
you are going to hear from, and they will give various
perspectives on this issue of pandemic flu. And certainly it is
an issue that everybody, I suppose, has their own point of view
on. And we will hear several points of view, I am sure, during
the course of this hearing today.
Our first panel of witnesses contain some faces and names
that are familiar to many of the members of this subcommittee.
First of all, Dr. Julie Gerberding, who is now a fellow North
Georgian, and I was going to brag about that until I heard from
Mr. Brown as to where you graduated from medical school, so he
is going to claim some credit for you as well. But being from
the CDC in Atlanta and the director of that facility, I am
certainly pleased to have you here today. Dr. Bruce Gellin, who
is the director of the National Vaccine Program Office within
the Department of Health and Human Services, pleased to have
you, Dr. Gellin. And Dr. Anthony Fauci, who is the director of
the National Institute of Allergy and Infectious Diseases
within NIH. We are certainly pleased to have all three of you
here today.
I am going to go ahead and introduce at this point the
second panel, and I have to extend an apology probably that I
won't be here for all of the second panel's testimony, but I
might if I don't have too many long-winded opening statements
here. I do have an engagement that is going to take me out for
a while, but our vice-chairman will be presiding at that time.
Dr. Marcia Crosse, who is the director of Health Care
Issues for the U.S. Government Accountability Office; Dr. Ralph
Tripp, who is the director for the Center for Disease
Intervention at the University of Georgia College of Veterinary
Medicine and the Georgia Research Alliance Chair of the Animal
Health Vaccine Development, and the second Georgian who is in
the panel group today; Dr. Andrew Pavia, who is chair of the
Taskforce on Pandemic Influenza at the Infectious Diseases
Society of America; and professor and chief of the Division of
Pediatric Infectious Diseases at University of Utah Health
Services Center and Primary Children's Hospital; Dr. Dominick
Iacuzio, close I am sure, medical director of the Hoffmann-La
Roche, Incorporated; Mr. Phillip Hosbach, who is vice president
of the Immunization Policy and Government Relations for sanofi
pasteur, which is the world's largest influenza vaccine
manufacturers.
So as you can see from the titles and the positions of the
members of these two panels, we certainly represent, I think, a
cross-section of the experts on this issue that we are facing
today.
All of us, I think, can attest to the fact that the fear of
a global influenza epidemic or a flu pandemic is certainly one
of the greater health challenges and threats that our country
faces and our world faces. All of us have different
perspectives on this. I have heard people, as we have talked
about having a hearing like this, saying that they remembered
the Asian Flu, they remembered the flu epidemics when they were
in college, and all of these things.
I have a resource that goes far beyond that, so I decided
to ask my 98-year-old mother and my soon-to-be 92-year-old
father-in-law what they remember about flu epidemics. And
remarkably, my mother, who was a young teenager in the 1918 flu
epidemic, recalls that she lost two aunts during that time. And
those of you who know the history of all this, this was a
serious flu that affected our country and affected the world.
My father-in-law went back even further than that. He
remembered a flu epidemic of the late 1800's and recalled that
there is a cemetery in our area where it is practically filled
with the victims of a flu from the late 1800's. So the idea
that this is something that is new is certainly not appropriate
because it is a threat that has hit our country and the world
in the past and is certainly a threat that we want to be sure
that we are as prepared as we possibly can be.
You might ask why the linkage with the veterinary
testimony. Part of it is the fact that my hometown calls itself
the poultry capital of the world, and we have for many, many
years, of course, been concerned with Avian Flu and the effects
on the poultry industry here and across the world. But there is
a direct linkage, as you will hear, in the threat and trying to
eliminate the threat within the poultry and fowl of the world
so that there is no transmission. So there is a linkage and we
certainly want to hear about that today.
With that, again, I welcome all of you and we look forward
to your testimony. And I will recognize my good friend, Mr.
Brown.
[The prepared statement of Hon. Nathan Deal follows:]
Prepared Statement of Hon. Nathan Deal, Chairman, Subcommittee on
Health
The Committee will come to order, and the Chair recognizes himself
for an opening statement.
I am proud to say that we have two expert panels of witnesses
appearing before us today that I believe will fairly represent the
different perspectives on this complex issue. We look forward to
hearing your testimony, and we are grateful for your cooperation and
attendance at today's hearing.
Our first panel of witnesses contains a few familiar faces to this
Committee:
Dr. Julie Gerberding, fellow North Georgia resident and Director of
the Centers for Disease Control and Prevention.
Dr. Bruce Gellin, Director of the National Vaccine Program Office
within the Department of Health and Human Services
Dr. Anthony Fauci, Director of the National Institute of Allergy and
Infectious Diseases within National Institutes of Health
Our second panel comes to us largely from outside of the federal
government and contains five experts witnesses:
Dr. Marcia Crosse, Director of Health Care Issues for the U.S.
Government Accountability Office
Dr. Ralph Tripp, Director of the Center for Disease Intervention at
the University of Georgia College of Veterinary Medicine and
Georgia Research Alliance Chair of Animal Health Vaccine
Development and our second witness hailing from North Georgia.
Dr. Andrew Pavia, Chair of the Task Force on Pandemic Influenza at
the Infectious Diseases Society of America and professor and
chief of the Division of Pediatric Infectious Diseases at the
University of Utah Health Sciences Center and Primary
Children's Hospital
Dr. Dominick Iacuzio, Medical Director for Hoffmann-La Roche, Inc.
Mr. Phillip Hosbach, Vice President of Immunization Policy and
Government Relations for Sanofi Pasteur, which is the world's
largest influenza vaccine manufacturer
As all of our witnesses today will attest, the threat of a global
influenza epidemic, or ``flu pandemic,'' is one of the greatest public
health threats we face today. From speaking to the experts in this
field, I truly believe that it is not a matter of ``if'' a flu pandemic
hits but ``when,'' and I believe that is our responsibility as Members
of Congress to ensure that the public is as protected from this threat
as possible. This, of course, is no simple matter and there is no
silver-bullet solution to this problem.
Protecting the public from the threat of a global flu pandemic
takes awareness of the potential threat as well as dedication and
cooperation from all of the involved organizations in both the public
and private sectors. Unfortunately, I believe we have ignored the
lessons of history and science and that we remain under prepared for
the emergence of a global flu pandemic that could potentially kill
millions of people over a short period of time and have irreparable
harm to our economy.
As most of you know, I live in Gainesville, Georgia, which is
considered to be the ``Poultry Capital of the World,'' and each year my
Congressional district produces over $915 million in farmgate value
from the poultry industry. If we were struck by a virulent strain of
the avian influenza virus, this entire industry would be completely
wiped out in matter of weeks.
Clearly, we have too much at stake to continue to largely ignore
this serious threat facing our society, and that is why I am excited
about the opportunity we have before us today to further explore the
potential threat of a pandemic flu and how we can better prepare to
ourselves to face this problem.
I am a great believer in the potential of science and human
determination and I firmly believe that if we dedicate ourselves and
our resources to solving this problem that we can overcome this
significant threat looming on our horizon.
Again, I welcome our witnesses and thank them for their
participation. I now recognize my friend from Ohio, Mr. Brown, for five
minutes for his opening statement.
Mr. Brown. Thank you, Mr. Chairman. Thank you to all three
witnesses, frankly, three of the most important people in our
government and our country. We welcome you to share your wisdom
with us and to thank you for your public service and the
terrific work you do for our healthcare system and especially
for our public health infrastructure.
In March, during a hearing on the National Institutes of
Health, the director showed the committee a slide charting the
increase and life expectancy in the United States over the last
century. That slide illustrated a number of things, including
the progress our country made in developing our public health
infrastructure and expanding healthcare coverage and access,
especially for seniors, and in fostering breakthroughs in
biomedical research.
Perhaps the most notable thing on the chart--other than the
30-year growth in life expectancy brought on mostly by public
health, secondarily by major high-tech medical breakthroughs--
but perhaps the most notable thing on the chart was the
downward spike in the year 1918. The last major pandemic flu
infected 28 percent of Americans, caused the deaths of nearly
700,000 people, as we know; worldwide killed in excess of 25
million people; some estimate as high as 50 million, more than
the first World War that ended that same year. Life expectancy
in our country dropped 12 years in 12 months. The example of
the early 20th century remains relevant today as a warning to
public health experts, to government officials, including
Members of this Congress who have absolutely inadequately
funded public health.
1918 shows how the spread of a flu strain that evades
available treatment lurks as one of the most serious risks to
our Nation's health. Our Nation and the international community
of which we remain vulnerable to flu strains that evade
available treatment and, as I said, can potentially wreak havoc
on the Nation's public health, obviously there are important
differences between 1918 and 2005. Many of those differences
are reflected in the makeup of our two panels today because of
the coordination and research led by CDC and NIH, our ability
to identify, prevent, and fight potentially harmful infection
is far superior to where we were early last century.
But along with this progress we face new challenges--a
world with seamless and constant global travel makes an
outbreak in the remotest corner of the world a threat to every
corner. When infection travels to Hong Kong to Hartford in a
matter of hours, it becomes significantly harder, obviously, to
contain.
Manmade treatments save millions but inadequate and
misapplied therapies have fostered new drug-resistant strains
of infection, especially a disease like tuberculosis. We have
seen a number of potential vaccine suppliers dwindle into the
single digits, and without adequate funding at the Federal,
State, and local level in large part because of decisions on
tax cuts and spending priorities made in this Congress, our
public health infrastructure is woefully unprepared to fight a
major outbreak and to deal with daily problems in public
health, in the deaths and the illnesses of people who most of
us on this panel, frankly, don't know--people in the inner
city, people afflicted by rural poverty.
These challenges resonated loudly last fall when it was
announced the U.S. would short nearly half of our expected flu
vaccine. I admire the word done by HHS and CDC to inform the
public and develop guidelines in the face of that shortage, but
we must apply the lessons learned last year and do it now. We
don't know whether we will face a pandemic, but we do know that
countless lives could be loss of a pandemic takes hold.
Epidemiologists and other public health experts are
currently tracking several potential flu pandemics, the Avian
Influenza, or Bird Flu, appears to pose the most lethal threat.
As of March, Avian Flu had killed 74 people in Asian and tens
of millions of birds. The global threat is a potential for the
virus to mutate and spread from human to human. The World
Health Organization has said that because of that possibility
the world is ``closer to an influenza pandemic than in any time
since 1968.'' WHO further points out similarities that suggest
Avian Flu could follow the same patterns as the strain that
caused the 1918 pandemic. The threat posed by Avian Flu is
great, but with the right investment and collaboration from
industry, academia, and government, a pandemic can be averted.
This committee should consider how best to ensure the
development, stockpile, and distribution of vaccine and
antiviral treatments. It must examine the avenues government
can take to bring competition and diversity back into the
vaccine market, ideally before a pandemic strain could hit our
shores. We should continue to work with partners like WHO to
fight infection where it exists and prevent worldwide
transmission. We should examine our Nation's investment in
basic research and better understand how that commitment
translates into more effective remedies for potential pandemic.
We should go beyond a discussion of pandemic flu and talk about
how and how much and how we should fund our public health
infrastructure, not just for major outbreaks that will affect
everyone, but the kind of day-to-day public health that,
frankly, the public health problems that our Congress and our
government, frankly, have so far been unwilling to address.
Thank you, Mr. Chairman.
Mr. Deal. We are pleased to have the chairman of our full
committee, Mr. Barton from Texas, and I recognize him at this
time for an opening statement.
Chairman Barton. Thank you, Mr. Chairman. I want to commend
you for holding this hearing. I want to commend both of our
panels of witnesses, the first panel and the second panel, for
being here on this important subject.
There are experts that say another killer flu epidemic is
inevitable. We don't know when or where it will begin or
exactly how many million that it will kill; we only know that a
pandemic flu has happened before, and we think that it almost
surely will happen again. Historically, influenza pandemics
have been deadly. With a world population of six-and-a-half
billion, even a relatively mild pandemic could kill millions of
people. In the United States the risk varies from tens of
thousands to hundreds of thousands. Put it like this: a bad flu
outbreak could kill more Americans than either or both of the
last two World Wars. It is probably fair to expect that some of
us in this room today would be sick and possibly a handful of
the people in this room would even die.
Right now we are monitoring some serious developments in
Asia concerning the recent Avian Flu strain. Both the World
Health Organization and the Department of Health and Human
Services has expressed serious concerns over these strains
developing into a global pandemic. Organizations around the
world and Health and Human Services in our country have taken
significant steps to mitigate the potential effects of
influenza pandemic.
That is the purpose of the hearing today is to do oversight
on those steps. I want to applaud the efforts in this country
in both the private sector and the public sector. I also want
to applaud the Secretary of Health and Human Services for his
emphasis on planning and preparedness for a pandemic flu and
his cooperation with international organizations.
In many other ways we do remain vulnerable. The global
vaccine industry is fragile. The capacity to gear up and
produce the necessary vaccines in the event of a pandemic is
limited. Liability concerns may hinder production and
distribution of any new vaccine. With ordinary flu vaccine
production already so low, the amounts that we can produce in
the face of a global pandemic are probably insufficient.
Moreover, the timeframes for development, production, and
approvals leave millions and millions of people vulnerable.
Antivirals may also be a countermeasure. We can place such
countermeasures in the national strategic stockpile, and I am
glad that we have done so with over two millions courses of
treatment so far.
But one question that we need to try to get an answer for
today is whether this is sufficient in the face of the apparent
threat. The amount in relation to population would appear to be
much less than what other countries are doing. I would also
note that many similar planning and preparedness activities
will be relevant in the face of bioterrorism and other emerging
threats. We need to work aggressively and cooperatively on all
of these issues.
Again, Mr. Chairman, thank you for the hearing. I look
forward to hearing from our witnesses today. And with that I
yield back.
[The prepared statement of Hon. Joe Barton follows:]
Prepared Statement of Hon. Joe Barton, Chairman, Committee on Energy
and Commerce
Thank you, Mr. Chairman. I commend you for holding this hearing on
this important public health issue.
Experts say another killer flu is inevitable. We don't know when or
where it will begin, or exactly how many millions it may kill. We only
know that a pandemic flu has happened before and it must surely come
again. Historically, influenza pandemics have been deadly. With a world
population of 6.5 billion, even a relatively mild pandemic could kill
many millions of people. In the United States the risk varies from tens
of thousands to hundreds of thousands. Think of it like this--a bad flu
outbreak could kill more Americans than either or both of the last
century's world wars. It is probably fair to expect that some of us in
this room today would be sick, and a handful of us would die.
Right now we are monitoring some serious developments in Asia
concerning a recent avian flu strain. Both the World Health
Organization and the Department of Health and Human Services has
expressed serious concern over these strains developing into a global
pandemic.
Organizations around the world and HHS have taken significant steps
to mitigate the potential effects of influenza pandemic. I applaud the
efforts that both the private sector and public sector are making to
address the potential need for different means of vaccine production. I
also applaud the Secretary of HHS for the emphasis on planning and
preparedness for pandemic flu and cooperation with international
organizations.
In many other ways, however, we remain very vulnerable. The global
vaccine industry is fragile and sparse. The capacity to gear up and
produce necessary vaccines in the event of a pandemic is limited.
Liability concerns may hinder production and distribution of any new
vaccine. With ordinary flu vaccine production so low, the amounts we
can produce in the face of a global pandemic are insufficient.
Moreover, the time frames for development, production, and approvals
leave millions vulnerable.
Antivirals may also be a useful countermeasure. We can place such
countermeasures in the National Strategic Stockpile. I am glad we have
done so for over 2 million courses of treatment, but I want to ask
whether this is sufficient in the face of the threat. The amount in
relation to the population appears to be much less than what other
countries are doing.
I note that many similar planning and preparedness activities will
be relevant in the face of bioterrorism and other emerging threats. We
will need to aggressively work on these issues. I look forward to
hearing from today's witnesses on this timely and important topic.
Mr. Deal. Thank you, Mr. Chairman. I am pleased to
recognize the gentlelady from California, Ms. Eshoo, for an
opening statement.
Ms. Eshoo. Thank you, Mr. Chairman, and good morning to you
and welcome to our very distinguished panel. It is always a
pleasure when you come to the committee to testify and I salute
you for your work on behalf of the American people. I think you
always distinguish yourselves.
The World Health Organization has warned that a pandemic
flu could occur at any time, which could cause deaths--as has
been stated by some of my colleagues already--in a range of two
to seven million people. Those are staggering numbers. I can't
help but think of--I don't know whether it was in the 1970's or
1980's--we saw something very common on people's desks, and it
said ``plan''--and then ``ahead'' kind of just fell off the
edge. So I think that today we are trying to plan ahead and be
wise, be prudent, and understand the factors that really didn't
come into play with the flu epidemic that we had in our own
country, the shortcomings that occurred, the lurch that people
found themselves in. And the best question that people asked
from senior centers and medical centers across the country was
why were we not prepared for this? Why hasn't this worked?
The Avian Flu, known as the Bird Flu, is the latest strain
of concern. Should it adapt fully to humans and be capable of
easy person-to-person transmission, it would probably spread
worldwide in 3 to 6 months.
Right now only about a dozen companies in the world make
flu vaccines. Many of these manufacturers are based overseas.
This is a serious problem for the United States if and when a
pandemic hits. In a pandemic, overseas manufacturers may be
reluctant to provide the United States with their stockpile,
and if they do agree to provide us with the vaccines, the FDA
will need the ability to rapidly evaluate the vaccine or agree
to let them in automatically once they are approved.
We also know that it is financially risky for manufacturers
to invest in research and development because the pandemic
strain that emerges may be substantially different from any
vaccine in development. There could likely be an investment
without any return.
So the Congress has to take steps to ensure that there is a
robust infrastructure for developing and providing vaccines and
treatments. We have to address the barriers that manufacturers
face. Today, I hope HHS will explain why their draft pandemic
flu plan is still not final, and I hope that the CDC can
explain why there has been a delay in stockpiling antivirals,
which, if taken within 2 days of getting sick, can reduce the
symptoms of the flu and shorten the time that one is sick by 1
or 2 days. Antivirals can make one less contagious to others.
So I look forward to the testimony from our expert panels
on this issue, and I hope that this committee will act quickly
and appropriately to prepare for pandemic flu. The American
people are counting on us to do that. Thank you, Mr. Chairman,
for holding this important hearing.
Mr. Deal. Thank you. I recognize the vice-chairman of the
subcommittee, Mr. Ferguson, for an opening statement.
Mr. Ferguson. Thank you, Mr. Chairman. Thank you for
holding this hearing and I thank our two panels of
distinguished guests today. I am looking forward to hearing
their testimony.
Mr. Chairman, we are staring down the barrel of a loaded
gun, and that gun is ready to fire. Expert after expert,
including the esteemed witnesses that we will hear from today,
have said that we must not ask if but when. When will we face
the strain of influenza virus that will cause a pandemic? And
when that happens, will we be ready?
We have heard these figures before but they are important
to repeat. In 1918 an influenza pandemic claimed the lives of
almost 600,000 Americans and more than 20 million people
worldwide. A little known fact to most people is that in a
regular flu season today kills about 36,000 Americans. Today,
public health experts at HHS and CDC estimate that an influenza
pandemic could cause 90,000 to 300,000 or more deaths in the
U.S. and tens of millions of people worldwide. Pandemic
influenza is nature's weapon of mass destruction. Even the
Homeland Security Department has weighed in on a flu pandemic's
effects, pegging the cost of a pandemic influenza outbreak in
just four cities in the United States at $70 billion to $160
billion.
Dr. Michael Osterholm, head of University of Minnesota's
Center for Infectious Disease Research and Police stated in the
``Wall Street Journal'' just this week that a pandemic flu
could trigger an economic crisis. Dr. Osterholm noted that the
2003 outbreak of SARS paralyzed cities and cost billions of
dollars even though its toll, 8,000 sick and 800 dead, was
relatively light. Pandemic flu could change the world
overnight, Dr. Osterholm stated, reducing or even ending
foreign travel and trade.
This problem demands our full attention and the full
commitment of our resources to counter a looming catastrophe.
Last November this Health Subcommittee held hearings as last
year's flu season was underway. Just a few weeks ago the
Oversight and Investigations Subcommittee held a perspective
hearing on the upcoming flu season and what we are doing to
ramp up vaccine production. But this hearing will be looking at
the threat of pandemic flu and our vital surveillance efforts
of Avian Flu strains in Asia, what is being done to ramp up
vaccine capacity once a pandemic strain is identified, and what
the response plan is while a pandemic is occurring,
specifically preparedness through stockpiling antivirals.
In each of the hearings we have had on the flu I have
stressed the importance of stockpiling antivirals to treat
those who are infected with the flu. Antivirals are a potent
way to combat a flu outbreak and are unique compared to
vaccines because they can be stockpiled for between 5 to 7
years, or perhaps more.
I look forward to hearing from our distinguished panels
today. I look forward to hearing their insight on how we can be
best prepared when the feared pandemic does in fact strike.
Thank you, Mr. Chairman. I yield back.
Mr. Deal. Thank you. Pleased to recognize gentlelady from
Colorado, Ms. DeGette, for an opening statement.
Ms. DeGette. Thank you, Mr. Chairman. Simply to say how
much I appreciate you having this important hearing. I will
submit my opening statement for the record and reserve my time
for questions.
Mr. Deal. I thank the gentlelady. Chair recognizes Dr.
Burgess for an opening statement.
Mr. Burgess. Thank you, Mr. Chairman, and I too want to
thank you for calling this hearing and thank the full committee
chairman and the ranking member for holding this hearing.
Looking at the historical significance of pandemic flu, it
is almost overwhelming to think about the challenges of
preventing a devastating outbreak of influenza and dealing with
the aftermath. The numbers are significant. In the last century
it is estimated that over 53 million people died from periodic
outbreaks of pandemic flu strains. Considering the world's
population is much more mobile today than at any time in our
history, I think the public health officials are right in
making the fight against communicable disease one of their
highest priorities. If we factor in the adaptability of the
influenza virus and the fact that an airplane makes a pretty
good way to communicate an illness like the flu, it is
understandable to see why we cannot consign the pandemic flu
outbreaks of the last century to the will-not-recur file.
There are tools available to us to confront a possible
outbreak, but the coordination, the surveillance, and the
prevention of a containment strategy are going to affect us at
the State, Federal, and, yes, at the global levels. The
severity of the next pandemic cannot be predicted, but even a
medium-level pandemic could cause between 100,000 and 200,000
deaths, almost three-quarters of a million hospitalizations,
and millions and millions of people in doctors' offices,
outpatient visits, and missing work. An estimated economic
impact would be well over $150 billion for a medium outbreak.
Not too long ago we were concerned about another
communicable disease, SARS virus. The SARS outbreak of 2003
exposed the capability of global surveillance and the
containment infrastructure as to how an outbreak of an unknown
disease can impact human interaction and commerce. And, Dr.
Gerberding, I thank you for tolerating my many phone calls over
that period. But even though the severity of the outbreak was
largely isolated to East and South Asian countries, it did
impact my district, which at the time was the home to the
Dallas/Fort Worth Airport. At the local level at least, the
SARS outbreak brought into sharp focus how fear can drive a
containment response to an illness in the absence of a workable
containment strategy.
The chairman brought up about the issue of liability and
the ranking member brought up about how we can assure the
development and availability of vaccines, and I too believe
that somehow controlling liability in the manufacture and
production of vaccines is going to be critical in our ability
to provide this on a larger scale.
But I look forward to hearing our panel today, and I
understand that our current capabilities of our public health
institutions and the vaccine industry will help improve our
response to any further pandemic outbreaks. Mr. Chairman, thank
you again, and I will yield back my time.
Mr. Deal. Thank you. Recognize the gentleman from Maine,
Mr. Allen.
Mr. Allen. Thank you, Mr. Chairman. I appreciate your
calling this hearing to examine the level of U.S. preparedness
for a possible flu pandemic. I look forward to hearing from our
expert witnesses on our current level of preparedness.
Unlike past flu pandemics, the relatively gradual emergence
of the Avian Bird Flu has given us time to ensure that we have
adequate resources to fight this deadly virus. At this point we
don't know when or if the current strain of Avian Bird Flu will
reach the U.S., but we do know that the epidemiology of the
H5N1 virus is more virulent and has already passed directly
from human to human. We know that this particular flu strain
has infected at least 92 adults in Vietnam, Thailand, and
Cambodia killing 52 people. We also know that there is
currently no vaccine for Avian Flu and no known cure.
I am concerned about our country's ability to develop,
approve, and secure adequate vaccine supplies. Today the U.S.
has one domestic source of flu vaccine. America has been a
world leader in developing life-saving medicines and
spearheading countless global health efforts. April 12, 2005
marked the 50th anniversary of the first polio vaccine. Polio
was eliminated in the U.S. because protecting the public's
health was perceived as a simple necessity, and every effort
was made to see that the vaccine would be freely distributed
and polio would be eradicated. Without diligent efforts to
maintain immunization programs here and strengthen them
worldwide, we would not be able to keep such deadly diseases at
bay.
The spread of the H5N1 virus poses a new challenge to the
U.S. scientific community and vaccine manufacturers. Many
experts have stated that we need a more reliable and flexible
vaccine production system, as well as improved surveillance and
public communication. Last year the license suspension of the
Chiron Company's vaccine manufacturing plant in the U.K. served
as a wake-up call. In addition to a shortage of supply, we were
faced with trying to educate the public about appropriate
distribution and who should be vaccinated first.
It is my understanding that countries such as Canada,
Japan, Australia, and New Zealand are stockpiling antiviral
treatments against pandemic flu for up to one-quarter of their
nation's population. The U.S. stockpile is currently maintained
for only 1 percent of our population, and I believe this
strategy needs to be reexamined.
I hope the witnesses will help us understand what went
wrong last year and what we can do to strengthen our domestic
vaccine supply, speed research and development, and establish
better distribution channels. Thank you again, Mr. Chairman,
and I yield back.
Mr. Deal. I thank the gentleman. Chair recognizes Mr.
Shadegg for an opening statement.
Mr. Shadegg. Thank you, Mr. Chairman, and thank you for
holding this important hearing on this topic. As my colleagues
have already noted, a pandemic flu could pose a very serious
health threat to not only our country but to the world. But it
should also be noted that it could also lead to an economic
crisis. Just yesterday a ``Wall Street Journal'' article noted
that ``A pandemic flu could sicken more than a billion people
and single-handedly stop travel and trade throughout the world,
resulting in untold economic losses.'' We have spent
considerable time and resources over the past few years
preparing for an attack of bioterrorism. Now, the lessons
learned from that experience should be used to address pandemic
flu.
The first and foremost of these lessons is that our best
defense is a strong offense. Preventing outbreaks through
vaccine development will ensure that a flu eruption fails to
reach pandemic status. I want to thank our witnesses for their
work and for their efforts to ensure that vaccines prevent
pandemic flu outbreaks, as well as for their testimony on what
we can do to meet the goals that we have set.
We also must be prepared, however, for an outbreak that
cannot be addressed through vaccination. In such an instance we
must have adequate surveillance systems to ensure early
recognition, sufficient communication tools, and networks to
enable response, and antiviral providers able to respond.
Again, Mr. Chairman, I thank you for sponsoring this
hearing and for your efforts in this regard. And I thank our
witnesses for their testimony and their work in this area.
Mr. Deal. Thank you. Recognize Ms. Baldwin for an opening
statement.
Ms. Baldwin. Thank you, Mr. Chairman. I too want to commend
you for holding this hearing today. I was wondering last night
as I began to read through the materials whether I would be
kept up all night by the dire threats. And as many of my
colleagues have noted, pandemic flu poses a serious threat to
our Nation and the world. A recent article in the science
publication ``Nature'' notes that a flu pandemic could cause 20
percent of the world's population to become sick, almost 30
million may need to be hospitalized, and a quarter of those
infected would die. And perhaps the most shocking aspect of
that article was that experts cited considered those numbers
optimistic.
Many experts are now saying that a pandemic flu occurring
in the United States is not a question of if but when. And in
our day of globalization when it takes mere hours to cross
continents, the old ways of containing an infectious disease
are no longer applicable.
While I am glad that the Department of Health and Human
Services has produced a draft of the Pandemic Influenza
Preparedness and Response Plan, I remain concerned about the
lack of progress on finalizing the report, and particularly, in
light of our crisis last fall when the delivery of vaccine for
seasonal flu was severely curtailed and only guidelines and
voluntary opting out by more healthy individuals helped us
address that crisis. It is imperative, I think, that we move
quickly and decisively, and we have some catching up to do.
I also note that experts stress again and again that our
planning efforts must be international in scope and look
forward to hearing from witnesses today on that aspect of our
planning efforts. There are several other aspects of our
preparedness that I hope to hear you address through your
testimony this morning. For example, I think we need to start
educating Americans, not just healthcare providers, but
American citizens need to know what to do in the case of an
outbreak, what their treatment and prevent options are, which
authorities to go to for information and what medications could
be available to them should an outbreak occur.
I also hope to hear your thoughts on the importance of
seamless communication, information sharing, and access to
resources among our healthcare professionals. The chain will be
only as strong as our weakest length and a public health nurse
in a rural county in Wisconsin must have the same access to
resources as a public health nurse in midtown Manhattan. Groups
and regions ought not to be place in competition with each
other.
If a pandemic flu should occur in the U.S., there will be a
terrific strain on our ability to provide medications as well
as treatments in our clinics and hospitals. If high numbers of
people get sick, who will decide who gets care in a hospital
when all the beds are full? Who gets placed in the ICU? Who
gets the last dose of an antiviral medication?
I look forward to hearing the witnesses today tackle some
of these very challenging questions. Thank you, Mr. Chairman. I
yield back.
Mr. Deal. Thank you. I too share the lady's concern. These
are rather frightening statistics. And from this point forward
nobody in the audience is allowed to cough, and if you do, the
hypochondriacs in our midst are going to leave the room. So I
am pleased to recognize Mr. Hall for an opening statement.
Mr. Hall. Mr. Chairman, thank you. And you would never get
Howard Hughes to shake hands with any of us here today, would
you? I thank you and I join the accolades of the other members
here to the Chair for holding this hearing and for other
hearings that he is very capable of holding and has held for
this committee and for this Congress.
You know, listening to the opening statements, and I will
be very brief because I don't have that much to say about it,
my children think I remember that 1918 Spanish Flu pandemic,
but I do remember and was affected by it because I knew people
that had lost children during that time. And when you lose
three-quarters of a million people in this country at a day and
time when we didn't have that many people in this country, that
was quite a loss and quite a huge percentage of people that
were affected by it.
I have said here and as I hear this I thought of a hearing
I held in the Science Committee some 4, 5, or 6 years ago on
asteroids. And we were all surprised to find out that an
asteroid had just missed the United States by about 15 minutes
in 1988, one the size of maybe Delaware or one of the other
States. We were a little surprised at that. We might also have
some surprises when we hear your testimony, because we don't
know by how much we have missed epidemics and what has been
done about it.
But I think we are very fortunate to have learned people
like you with your years of study and your research on vaccines
and for things to do for it, that you have prepared yourself
for prevention, and if not prevention, control. I thank you for
giving your time and I think that it is a timely thing that we
need to hear and need to know more about. Mr. Chairman, I thank
you for having it. I yield back my time.
Mr. Deal. I thank the gentleman. Recognize the gentleman
from California, Mr. Waxman, for an opening statement.
Mr. Waxman. Mr. Chairman, I thank you for calling this
hearing today and drawing attention to this very important
issue. Many leading scientists believe that it is not a matter
of if but when the next flu pandemic will hit. It has been
estimated that even a medium-level pandemic could cause up to
200,000 deaths in the United States and 734,000
hospitalizations at a cost of up to $166 billion. Pandemic flu
is a grave public health threat, and we must do all we can to
get ready for it.
There are many unknowns surrounding the pandemic flu. It is
unknown which strain of the flu virus would cause the pandemic,
so production of an effective vaccine must wait until the
pandemic begins. It is unknown how long it will take to produce
a vaccine. It is also an unknown whether or how well antiviral
medications will work. With so many unknowns it is easy to
become very anxious about this topic. Fortunately, there are
some things we do know, and these are some steps we can take
now to be prepared no matter what the strain of the pandemic
virus, no matter how long it takes to make a vaccine, no matter
how well antiviral medications work, our core public health
system must be strong. We must have a way to deliver vaccines
to those most at risk quickly and efficiently.
This year's flu shortage illustrated how far away we are
from this capability. Many chronically ill and elderly
Americans were forced to wait for hours just to get their
vaccines. We must do better than this. We also must have the
ability to maintain core public health functions in the event
of a pandemic. One major vaccine manufacturer has told us that
in order to produce the necessary vaccines to combat a flu
pandemic, the company would have to dramatically curtail
production of its childhood vaccines. This would be a
particularly dangerous situation given that stockpiles of many
childhood vaccines do not exist. It would be a disaster if our
preparation for flu pandemic led to outbreak of childhood
diseases. But that could happen.
That is why today we must do more than ask our expert
witnesses to speculate about uncertainties. We must also ask
some tough questions about the administration's response to the
challenges as plain as day. We also must ask why the
administration has proposed major cuts in funding for key
programs in State and local preparedness. These are the very
programs that allow our communities to prepare for
bioterrorism, natural disasters, and a flu pandemic. We must
also ask why the administration has yet again failed to provide
adequate funding for States for vaccines against preventable
diseases. If we cannot even stop bacterial meningitis from
spreading in our communities even when we have vaccines, how
will we stop the flu virus? And we must ask why it has taken so
long to get senior administration officials to focus their
attention on lack of stockpiles for routine pediatric illness.
These stockpiles were promised 3 years ago, and yet a letter
asking about the holdup was sent to vaccine manufacturers just
2 days ago.
After we ask these tough questions it will be time to get
back to work, and I hope we can join together across party
lines to support major improvements in our public health
system. I thank the witnesses for attending and look forward to
their testimony.
Mr. Deal. Recognize the gentlelady from California, Ms.
Bono, for opening statement.
Ms. Bono. Thank you, Mr. Chairman. I will waive my opening
statement.
Mr. Deal. Recognize Mr. Green from Texas for an opening
statement.
Mr. Green. Thank you, Mr. Chairman, and thank you and the
ranking member for holding the hearing on the threat of
pandemic flu and the steps we are taking to protect Americans
from the outbreak. Hopefully, we will get ahead of the curve. I
also want to thank our panelists this morning who--as a lot of
us feel like--listen to us give our statements, but oftentimes
it is the only time members on the committee can do anything
except vote.
I have a personal interest in this issue because my
daughter has been accepted in a medical fellowship on
infectious diseases, and so I am particularly thankful that I
can gain some knowledge in one of the issues that she certainly
is working with now in the forefront of her medical work. I
tell her I don't want to be treated for anything she studies.
The 20th century was a witness to three flu pandemics, so
we know what kind of destruction these outbreaks can cause. And
recent press reports suggest we are dangerously close to
witnessing another. According to the World Health Organization,
the next pandemic flu would likely result in 1 to 2.3 million
hospitalizations and 300 to 650,000 deaths in developed
countries alone. We can only imagine the kind of havoc that a
pandemic flu would wreak on developing nations which do not
have the healthcare infrastructure surveillance capabilities to
protect their citizens from infectious disease.
Where I ought to know this is to be the case is poor
countries facing the threat of the Bird Flu since the current
outbreak in 2003 have been unable to successfully detect and
respond to individual cases of Bird Flu. The influenza strain
that most concerns infectious disease specialists is the H5N1
strain has jumped from animals to human and to date has killed
36 people in Vietnam, 12 in Thailand, and four in Cambodia. And
while the Bird Flu has thus far been contained in Asia, the WHO
influenza specialists recognize this can't last that long with
the amount of contact we have literally in our very small world
now.
We know that human flu pandemic will consist of three
elements in tandem. The Bird Flu has already presented us with
a virus to which humans have little or no immunity. The deaths
in Asia have proven that this virus can replicate itself in
humans causing serious illness, if not death. The virus may
also be transmittable from human to human. Since this current
outbreak in 2003, the third element has not been met. However,
Dr. Fauci's testimony today indicates a high probability where
they not have witnessed at least once case of human-to-human
transmission in H5N1 virus. Given this news, the hearing is
particularly timely. The subcommittee has held hearings in the
past about our supply of flu vaccine in this country and the
challenges that face both the government and the vaccine
manufacturers. This hearing, I hope, will build on previous
knowledge we gained from our subcommittee's activities and shed
light on steps we must take to ensure an adequate and effective
vaccine supply to protect Americans from the deadly flu
pandemic.
And, again, I would like to thank our witnesses for being
here and for what you do every day to protect our constituents.
Thank you, Mr. Chairman.
Mr. Deal. I thank the gentleman. We are ready now for our
first panel and--well, I have another member. Mr. Pitts, do you
wish to make an opening statement? All right. You have already
heard everything that we know about this issue. Now we are
looking forward to hearing what you know about it. I would
remind you we have your written testimony, which is a part of
the record. And, Dr. Gerberding, we will start with you.
STATEMENTS OF JULIE L. GERBERDING, DIRECTOR, CENTERS FOR
DISEASE CONTROL AND PREVENTION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES; ANTHONY S. FAUCI, DIRECTOR, NATIONAL INSTITUTE OF
ALLERGY AND INFECTIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH,
DEPARTMENT OF HEALTH AND HUMAN SERVICES; AND BRUCE G. GELLIN,
DIRECTOR, NATIONAL VACCINE PROGRAM OFFICE, DEPARTMENT OF HEALTH
AND HUMAN SERVICES
Ms. Gerberding. Thank you. I am absolutely grateful to the
committee for having this hearing. I think the more we shine a
bright light on this problem, the more we will be able to be
prepared to handle it. Your eloquence in describing both the
severity of the threat as well as the impact is heartening. And
I think I speak for all of us in the Department of Health and
Human Services and Secretary Leavitt, we know this is a high
priority for the agency. Secretary Leavitt has been meeting
with us almost every day on flu since he took office. And at
the World Health Assembly last week where all of the leaders of
the health community around the globe assembled in Geneva, the
secretary convened several discussions on influenza pandemic
planning and how we could assist.
What I am going to try to do today is two things in my
brief remarks: one is just give a capsule situation report on
the flu in Asia, and second, describe in brief some of the
important steps that we are already taking. We are not waiting
for that final preparedness plan to get approved. We are acting
now to get the show on the road.
Just as a reminder for those who aren't familiar with
influenza, you will be hearing us talking about H5N1 or H3N2.
Flu is a simple little virus with just a few genes. One of them
codes for something called ``H'' or hemagglutinin and the other
codes for ``N'', neuraminidase. But despite its simplicity,
this is a very sinister virus, and it changes all the time.
When the changes in H and N are little or small in genetic
context, it is called a drift, and that is what happens every
year and why we need to get a new flu shot every year.
Sometimes we see a shift, which is a major change. Usually the
virus exchanges genes with some other strain of flu and you see
a big jump in the composition in the H or the N, and that is
the change that is usually associated with pandemics.
[Chart]
Ms. Gerberding. This is a map of the prior influenza
pandemics that have occurred throughout the last 100 years, and
you can see that each time there is a big shift in the H gene
from H1 to H2; the Asian Flu appeared when H2 came on the
horizon. When H3 appeared we saw the Hong Kong Flu pandemic.
And what you are seeing in upper corner here are H7, H5,
and H9, which are Avian isolates not yet transmitted in broad
scale to people in pandemics, but certainly on the horizon and
very ominous because we, of course, have no population immunity
to any of those H's. And so because we are seeing right now H5
and 1 in Asia, we are particularly concerned about the
emergence of the virus in a world that has absolutely no
immunity.
How do these big jumps occur? Well, it is a complicated
story, but often what happens is that a virus from a bird
host--in this case an asymptomatic duck, or in Asia right now,
the poultry that are infected--can commingle in a pig usually
with a human virus and exchange those big genes resulting in a
completely new virus that then gets transmitted to people. But
in this context in Asia today, we are also concerned about the
direct transfer of the poultry virus to humans. And this, we
know, has occurred a number of times.
The reason this is so critical and why we are focusing so
much on Asia is that in China alone there are 1.3 billion
people, but there are 13 billion chickens and about 508 million
pigs. So in that area of the world if you multiply that by the
incredible density of population, we are sitting on the
cauldron of flu virus incubation, and the threat is certainly
one that we are taking very seriously.
These are the numbers of people so far who have been
reported to the World Health Organization with this H5N1 Avian
Flu: 97 people in total with a fatality rate of 55 percent.
This may be the tip of the iceberg; we don't know. But it
certainly is a cause of concern. And recently there has been
some suggestion of more clustering in at least one region of
Vietnam and perhaps the suggestion that the virus is slowly
becoming more adaptable to humans. Of course, that remains to
be seen.
This map shows some of the indicators of poultry virus
activity in this region. I have occluded status: unknown here
as China because just this week we learned about the migratory
bird die-off in Western China, which was related to a species
of geese called the Bar-headed Goose that migrates up from
India and the Tibetan Plateau, and a reliable laboratory in
China has indicated that that indeed was H5N1 virus.
So we are seeing mass populations of poultry throughout
Asia infected. And all of the activities that we are doing
right now at HHS are targeting, first and foremost,
preparedness in that region. We are very pleased with the
recent supplemental appropriation from Congress for CDC and
USAID to receive $25 million to step up activities in Asia and
another $58 million to augment our supplies in preparation for
the stockpile.
But we are doing a lot of other things at CDC and HHS as
well. We are utilizing all of our laboratory networks, we are
developing rapid diagnostic tests, we are working on expanding
our capacity for vaccine seed development, our virus genomic
activities to characterize these strains and their drug
susceptibility, and certainly Dr. Fauci will talk about how all
that feeds into vaccine development.
Last, just let me mention that this map of the various
teams of people at CDC is just a microcosm of what is gong on
throughout HHS and the entire public health system. We are
working with all sectors, including public health, healthcare,
business, and communications experts, but we are also taking
advantage of the $287 million in appropriation that we did
receive this year to support flu activities in our agency.
Those appropriations are being used to purchase influenza
vaccine, to purchase antivirals for influenza from the
department, to support improvements in the vaccine
manufacturing and science, as well as many other investments to
help speed and accelerate our preparedness for this very
uncertain virus.
So we look forward to answering specific questions about
the steps that we are taking, the preparedness, but I wanted to
assure that, again, we are not waiting for a written plan; we
are acting now to do everything we can with the resources that
we do have. And we are particularly focusing those resources on
Asia where we feel the imminence of the situation is probably
deserving of our greatest attention. Thank you.
[The prepared statement of Julie L. Gerberding follows:]
Prepared Statement of Julie L. Gerberding, Director, Centers for
Disease Control and Prevention, U.S. Department of Health and Human
Services
Mr. Chairman and members of the Subcommittee, I am pleased to be
here today to describe planning and preparedness for an influenza
pandemic, including the potential threat posed by the H5N1 avian
influenza virus currently in Asia. Department of Health and Human
Services Secretary Mike Leavitt has made influenza pandemic planning
and preparedness one of his top priorities; and each agency within the
Department is working together to prepare the United States for a
potential threat to the health of our nation.
I will discuss steps the Centers for Disease Control and Prevention
(CDC) is taking with many partners both domestically and globally. The
strength and flexibility of CDC and other components of the public
health system are vital assets as the United States sharpens its
readiness for an influenza pandemic. Although we have made significant
progress, more work is needed, particularly in the areas of
surveillance capacity and response, and the development of potential
vaccines. Increased public awareness and understanding about infection
control, containment, and other actions also are important in
preparation for an influenza pandemic.
PANDEMICS IN PERSPECTIVE
Seasonal influenza causes an average of 36,000 deaths each year in
the United States, mostly among the elderly and nearly 200,000
hospitalizations. In contrast, the actual severity and impact of the
next pandemic, whether from H5N1 or another influenza virus, cannot be
predicted. However, modeling studies suggest that, in the absence of
any control measures, such as vaccination, a ``medium-level'' pandemic
in the United States could result in 89,000 to 207,000 deaths, between
314,000 and 734,000 hospitalizations, 18 to 42 million outpatient
visits, and another 20 to 47 million people being sick. Between 15
percent and 35 percent of the United States population could be
affected by an influenza pandemic, and the economic impact in our
country alone could range between $71.3 and $166.5 billion.
A public health response to a disease of this magnitude involves
numerous challenges.
A pandemic can occur any time during the year and can last much
longer than seasonal influenza.
In more advanced pandemic phases, the capacity to prevent or control
transmission of the virus can become extremely difficult.
Although the primary concern at present is the H5N1 avian influenza
strain in Asia, an outbreak leading to a pandemic can occur
anywhere in the world and may derive from viral strains of
influenza other than H5N1.
Comparing the onset and spread of the next pandemic to those of the
20th century is problematic for many reasons, including changes
in population and social structures, medical and technological
advances, and the increase in international travel.
With zoonotic diseases such as avian influenza, there is a need for
coordination with the animal health community.
THE CURRENT SITUATION IN ASIA
For an influenza virus to cause a pandemic, it must meet three
major criteria: (1) possess a new surface protein to which there is
little or no pre-existing immunity in the human population; (2) be able
to cause illness in humans; and (3) have the ability for sustained
transmission from person to person. So far, the H5N1 virus has met two
of these three criteria, but it has not yet shown the capability for
sustained transmission from person to person.
Concerning this third point, it is important to keep in mind the
close relationship of viral infections in animal hosts and those in
humans. Ongoing dialogue between agricultural and public health
officials is extremely important for the careful, consistent
surveillance necessary in both animal and human populations. Although
the present avian influenza H5N1 strain in Asia does not yet have the
capability of sustained person-to-person transmission, chicken-to-human
transmission has occurred, and in at least one cluster, limited person-
to-person transmission has been identified. As of May 19, 2005 the
World Health Organization (WHO) had confirmed 97 cases of H5N1
influenza in humans since January 28, 2004, with a case fatality rate
of 55 percent. The World Organization for Animal Health (OIE)
confirmed, as of May 13, 2005, that H5N1 had been found in animals from
nine Asian countries in 2004 and 2005, with especially large outbreaks
among animals in Vietnam and Thailand. Millions of domestic birds have
been culled in attempts to stop the spread of the virus among animal
populations.
Although human case fatality rates seem to have gone down somewhat
since February 2005, CDC, WHO, and other partners are still quite
concerned for several reasons. The H5N1 strain now appears to be
endemic in poultry and other birds in a number of Asian countries,
signaling a potential long-term threat of mutation and reassortment
with other viral strains. Recent studies have found that ducks carry
the H5N1 strain asymptomatically, making it difficult to monitor the
magnitude of transmission from ducks to other species. Confirmation
that H5N1 also has been transmitted to mammals is a particular concern,
because of the increased potential of the strain to reassort with other
strains already common to humans and other mammals. Studies have
documented highly pathogenic H5N1 in pigs, tigers, and leopards in
Asia. Difficulties in implementing effective in-country surveillance,
including enhancing the training of laboratorians, epidemiologists,
veterinarians, and other professionals, inhibit the type of
comprehensive reporting that is essential to monitor H5N1 and other
strains of highly pathogenic avian influenza. Finally, changes in the
epidemiology of the infections, such as decreasing mortality rates,
could indicate changes that make the viruses better adapted to humans.
Additional studies and research are needed to better understand the
current situation and how the viruses may be changing.
RESPONDING TO A PANDEMIC
An effective response to an influenza pandemic requires highly
collaborative planning, implementation, and flexibility in resolving
issues at many levels. The Department of Health and Human Services
(DHHS) is leading the coordination of preparedness efforts through its
Pandemic Influenza Response and Preparedness Plan, which was released
in draft form in August 2004 for public comment and is under revision.
In addition, states are either developing pandemic influenza plans or
revising existing plans to reflect new information and data. Key
elements of these plans include surveillance, infection control, use of
antiviral medications, community containment measures, vaccination
procedures, communications, and ability to sustain essential services
in times of widespread illness. Similar elements inform a plan that CDC
is developing, that will provide detailed guidance and materials to
states and localities and will complement the DHHS plan. CDC also will
take the lead in working with the Advisory Committee on Immunization
Practices and the National Vaccine Advisory Committee to prioritize
recommended target groups for use of antiviral medications and vaccines
during a pandemic when supplies are limited.
Once a pandemic strain starts circulating in the United States,
isolation precautions for persons who are ill and quarantine for
persons exposed may need to be considered to limit the early spread of
pandemic influenza, particularly before a vaccine becomes available.
Measures such as these will require a multi-level, multifaceted, staged
process, such as evaluating all ill travelers arriving from affected
areas. On April 1, 2005 the President amended Executive Order 13295,
adding influenza caused by novel or reemergent influenza viruses that
are causing, or have the potential to cause, a pandemic to the list of
quarantinable diseases. CDC has implemented a series of travel notices
to minimize the potential for outbreaks to extend to wider geographic
areas. CDC also has expanded the number and capacity of its quarantine
stations at major ports of entry into the United States. As with any
quarantine, such activities need to be undertaken judiciously to
minimize adverse impacts on civil liberties.
Vaccination is the best long-term strategy for influenza prevention
and control, both during annual outbreaks and a pandemic; antiviral
medications provide an earlier, secondary line of defense. Other
measures may help control the spread of influenza in a pandemic
situation, such as isolation of ill persons and quarantine of healthy
exposed persons. Comprehensive preparedness for annual influenza
outbreaks is a vital component of an effective response to pandemic
influenza, although pandemic planning will require additional
preparation activities.
SURVEILLANCE
The United States, working domestically and with global partners,
needs to expand the scope of early-warning surveillance activities used
to detect the next pandemic. We cannot estimate the amount of time from
first detection in another country to peak disease in the United
States, but it could be a matter of months or less. Time will be of the
essence in making sure we can produce, test, and administer vaccine as
quickly as possible. It will take several months for the first dose of
pandemic vaccine to be ready and longer to manufacture enough to
vaccinate the entire U.S. population. Therefore, vaccine will be in
short supply at the start of the pandemic. Under the most favorable
conditions, by the time the first dose of vaccine would be given to the
first person, many others will have already become ill or died. For
this reason, surveillance to monitor ongoing changes in the H5N1 strain
of avian influenza currently causing human infections and to monitor
for other viruses with pandemic potential is needed to develop
prototype vaccine candidates as quickly as possible. Further, because
such a pandemic strain can arise anywhere, at any time, expanded global
surveillance capacity is needed.
The outbreaks of avian influenza in Asia have highlighted several
gaps in disease surveillance globally that the United States must help
address to improve our ability to prepare for an influenza pandemic.
These challenges include: (1) lack of infrastructure in many countries
for in-country surveillance networks; (2) need for increased training
of laboratory, epidemiologic, and veterinary staff; and (3) resolution
of longstanding obstacles to rapid and open sharing of surveillance
information, specimens, and viruses among agriculture and human health
authorities in affected countries and the international community. CDC
and HHS have made significant progress in the past year toward
enhancing surveillance in Southeast Asia. This initiative needs to
continue at both national and international levels if we are to expand
geographic coverage and develop an adequate capacity to conduct
effective surveillance. These efforts, in turn, will increase our
ability to detect new variants earlier, make more informed vaccine
decisions for yearly epidemics, and build an ``early warning system''
for new viruses that may cause a pandemic. With the ever-present threat
of the emergence of a new pandemic strain, we need to know what is
happening in the backyards of Southeast Asia, as well as elsewhere
throughout the world. Year-round, world-wide surveillance for
infections of humans with new strains of influenza is essential for us
to prepare for the next pandemic, as well as for next year's epidemic.
Recently, the Congress passed and the President signed an FY 2005
Emergency Supplemental Appropriations Act for Defense, the Global War
on Terror, and Tsunami Relief, which included $25 million in
international assistance funds to prevent and control the spread of
avian influenza in Southeast Asia. These funds will support human
surveillance, laboratory capacity, and enhanced knowledge of state-of-
the-art avian influenza laboratory and field techniques in Southeast
Asia.
In the past year, CDC has considerably improved domestic
surveillance, adding two new major components to our surveillance
system. We worked with the Council for State and Territorial
Epidemiologists (CSTE) to make confirmed pediatric deaths from
influenza nationally notifiable, and we implemented hospital-based
surveillance for influenza in children at selected sites. To further
improve our understanding of the impact of influenza on severe
outcomes, such as hospitalization, we are working with the CSTE to make
all laboratory confirmed influenza hospitalizations notifiable. We have
issued interim guidelines to states and hospitals to enhance
surveillance for potential cases of people infected by avian influenza
on several occasions and these enhancements continue. CDC also set up
special laboratory training courses for identification of avian
influenza using rapid molecular techniques. So far, professionals from
48 states and Washington D.C. have been trained.
However, to be as prepared as possible for a pandemic, we are
working to do much more in the domestic surveillance arena. The United
States is working to: (1) ensure that states have sufficient
epidemiologic and laboratory capacity both to identify novel viruses
throughout the year and to sustain surveillance during a pandemic; (2)
improve reporting systems so that information needed to make public
health decisions is available quickly; (3) enhance systems for
identifying and reporting severe cases of influenza; (4) develop
population-based surveillance among adults hospitalized with influenza
and (5) enhance monitoring of resistance to current antiviral drugs, to
guide policy for use of scarce antiviral drugs.
MANAGING THE VACCINE SUPPLY
During an influenza pandemic, the presence of U.S.-based
manufacturing facilities will be critically important. The pandemic
influenza vaccines produced in other countries will likely not be
available to the US market as those governments may prohibit export of
the vaccines produced in their countries until their domestic needs are
met. However, the vaccine manufacturing system in the United States is
fragile. Currently, there are only three influenza vaccine
manufacturers producing vaccines for the US market, and only one
produces its vaccine entirely in the United States.
During the past several years, CDC and other DHHS agencies have
developed several new strategies to address annual influenza outbreaks,
including the support of enhanced vaccine production, and have worked
to ensure a better match of vaccine distribution to the populations in
greatest need. Public demand for influenza vaccine on a yearly basis
needs to be both stabilized and increased, so that companies will have
a growing market to provide an incentive to increase production. These
strategies include $40 million for purchasing influenza vaccine for the
pediatric stockpile to protect against annual outbreaks of influenza,
and $30 million will be used for contracts to expand the production of
bulk single-strain influenza vaccine for use if needed during annual
influenza season or possibly in a pandemic situation. In addition, the
President is requesting $120--million in fiscal year 2006, an increase
of $21 million, to encourage greater production capacity that will
enhance the U.S.-based vaccine manufacturing surge capacity to help
prepare for a pandemic and further guard against annual shortages.
The Department also appreciates the inclusion of $58 million in the
FY 2005 Emergency Supplemental to procure additional influenza
countermeasures for the CDC Strategic National Stockpile (SNS) in FY
2005. Currently, the SNS has enough oseltamivir (Tamiflu) capsules to
treat approximately 2.26 million adults and oseltamivir (Tamiflu)
suspension to treat more than 100,000 children. In addition, SNS
contains enough rimantadine tablets to treat up to 4.25 million people
and enough rimantadine suspension to treat up to 750,000. It should be
noted, however, that oseltamivir is the only antiviral at this time
shown to be effective against the H5N1 avian influenza virus in Asia.
In addition, SNS funds have been used to purchase approximately 2
million bulk doses of unfinished, unfilled H5N1 vaccine, although it is
not yet formulated into vials nor is the vaccine licensed. Clinical
testing to determine dosage and schedule for this vaccine began in
April 2005 with funding from the National Institutes of Health.
DHHS also is supporting the development and testing of potential
dose-sparing strategies to extend a given quantity of vaccine stock.
Regarding annual influenza vaccination, there is an emerging
consensus that it is desirable to expand vaccine coverage beyond the
high priority groups for whom routine vaccination is already
recommended. Discussions are under way to review the data that would be
needed to consider broadening recommendations for influenza
vaccination. CDC is developing strategies to increase informed demand
for, and access to, influenza vaccine for persons who are currently
recommended to be vaccinated each year. For example, according to a
2003 Institute of Medicine report, an estimated 8.2 million additional
high-risk uninsured adults 18-64 years old warrant annual vaccination.
We recognize that these at-risk persons need better access to vaccine
during a pandemic as well as for seasonal influenza.
Additionally, CDC, in conjunction with the Advisory Committee on
Immunization Practices, is developing an internal set of possible
influenza vaccine supply scenarios that may occur in future influenza
seasons and during a pandemic. These scenarios range from worst-case to
best-case situations and are an important part of CDC planning efforts.
We are preparing recommendations, plans, and communication messages for
any of the possible situations.
CONCLUSION
Although the present avian influenza H5N1 strain in Southeast Asia
does not yet have the capability of sustained person-to-person
transmission, we are concerned that it could. CDC is closely monitoring
the situation in collaboration with the World Health Organization. CDC
is using its extensive network of partnerships with other federal
agencies, provider groups, non-profit organizations, vaccine and
antiviral manufacturers, and state and local health departments to
enhance pandemic influenza planning. Our responses to the annual
domestic influenza seasons also will inform the nation's planning and
preparedness for pandemic influenza. The same laboratories, health care
providers, surveillance systems, and health department plans and
personnel guide both responses. These actions, in conjunction with
increased public understanding about influenza, will help us all
prepare for an influenza pandemic.
Thank you for this opportunity to share this information with you.
I am happy to answer any questions.
Mr. Deal. Thank you. Dr. Fauci.
STATEMENT OF ANTHONY S. FAUCI
Mr. Fauci. Thank you very much, Mr. Chairman, and thank you
for giving me the opportunity to address this committee on the
research component of the department's effort in preparedness
against pandemic flu.
[Slide]
Mr. Fauci. I would like to put this into perspective by
showing you first this initial slide, which shows the
complimentary roles of the sister agencies within HHS regarding
how we approach pandemic flu preparedness. Dr. Gerberding has
explained to you the CDC's role. The FDA plays an important
regulatory role, particularly with regard to the countermeasure
that are used, both therapeutics and vaccines. I am going to
spend my couple of minutes describing for you some of the
research endeavors that range from fundamental basic science up
through and including the development of countermeasures. All
of this, of course, is coordinated under the office of Public
Health Emergency Preparedness at the department.
This slide illustrates the multifaceted component of the
research endeavor. You see on the lower-left we refer to a
surveillance and epidemiology, which is really fundamentally
the CDC's role. We play a very small role in that, and that is
at the molecular level to try and characterize the evolving,
changing viruses, particularly those that occur in animal
species, as just described by Dr. Gerberding.
In addition, we train and provide both physical and
intellectual capacity and, importantly, the basic research
understanding of the virus and how it works helps us in our
endeavor to make vaccines, therapeutics, and diagnostics.
I am going to spend just a moment describing two examples
of some of the basic approaches toward influenza which have
helped us in the development of vaccines. Some of you may have
heard of the terminology ``reverse genetics.'' What that is is
a molecular sophisticated way to take away some of the
uncertainty of providing that seed virus that you need to make
a vaccine. What it does is deliberately take the genes from a
virus that we know grows very well in our egg cultures and then
ultimately, hopefully, some day in cell-based cultures, as well
as the important genes from the index virus in question--in
this case it is an H5N1--and deliberately put them together to
predictably get the seed virus that will be used for the
vaccine. And in fact this is just what we did with the H5N1
that is currently in clinical trials, as I will describe to you
in a moment.
Another research endeavor is that which we are doing in
collaboration with the CDC and industry is to provide a
consistent way to get cell-based cultures to ultimately
transition and replace the egg-based cultures. And the reason
for that is that the surge capacity of having the ability to
grow cells in culture all year round so that if you either have
to change direction or surge up in numbers, that system is much
more adaptable than the egg-based system, which has its very
good, positive points.
Having said all of this, and I hope we get into the
discussion, that despite the effort, despite the research, the
capacity globally to make vaccines for H5N1, as several of the
members have alluded to, is really one of the great limiting
issues that we have to face, and I hope we get back to that.
Let me just spend a moment talking about the influenza
vaccine trials. Dr. Gerberding mentioned and I want to
underscore that we are not waiting for anything to move ahead
to address this problem. We have an H5N1 from Vietnam and we
have a trial that has already yielded data. There are two major
trials. The inactivated vaccine trial began on April 4, 2005 in
three medical centers in the United States. It is in multiple
stages involving four doses, a prime initial vaccine, followed
by a boost. The reason we have to do that when we don't
generally have to do that with the seasonal vaccine that we
change a bit every year is that our population, or the
population of the world, has never experienced an H5N1. So we
don't really know what the proper dose is or whether or not we
are going to need, and we likely will need, a prime and a
boost. So we have divided the trial into stages. We fully
enrolled the first 118 adults in Stage 1; we fully enrolled the
second stage for a total of 450. By early to mid-summer we will
have safety data and data about how to use that, what is the
right dose, and then we will move onto the elderly--greater
than 65--and then we will go to children.
There is also an H9N2 trial going as well as attenuated
vaccine trials. So there are multiple things going ahead, and
we are clearly ahead of any other country in the trial of the
relevant H5N1 right now.
Again, just a word on antiviral therapy. We know that H5N1
is sensitive to oseltamivir and relatively resistant to the
other class of drugs. We are doing research both in
understanding how best to use the existing drugs alone or in
combination in adults and in children, as well as targeting
other targets of the influenza replication cycle so that we
will have a pipeline of drugs should resistance emerge.
And finally, just to recapitulate and underscore that the
NIH research effort is fundamentally based on basic research
but is rapidly applying that to the development of
countermeasures, particularly in the form of vaccines and
therapeutics that will be part of the broad Department of
Health and Human Services Pandemic Preparedness Plan. I would
be happy to answer your questions later. Thank you very much,
Mr. Chairman.
[The prepared statement of Anthony S. Fauci follows:]
Prepared Statement of Anthony S. Fauci, Director, National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services
INTRODUCTION
Mr. Chairman and Members of the Committee, thank you for the
opportunity to discuss with you the role of the National Institutes of
Health (NIH) in preparing the Nation for the next influenza pandemic.
The Department of Health and Human Services (DHHS) Draft Pandemic
Influenza Preparedness and Response Plan outlines a coordinated
national strategy to prepare for and respond to an influenza pandemic,
and assigns specific roles to various Federal agencies; the National
Institute of Allergy and Infectious Diseases (NIAID) holds the primary
responsibility for carrying out those duties assigned to NIH.
In this capacity, NIAID provides the scientific input required to
facilitate the development of both new influenza vaccine technologies
and novel antiviral drugs against influenza viruses. Under this
Administration, we have made extraordinary progress. DHHS began
investing in new technologies, securing more vaccines and medicines,
and preparing stronger response plans. Total NIH funding for influenza
research has grown more than five-fold in recent years, from $20.6
million in FY 2001 to an estimated $119 million in FY 2005. This is
part of the largest investment ever made by the Federal government in
protecting against influenza.
Influenza epidemics typically occur during the winter months in the
United States and other temperate regions of the world and cause
significant morbidity and mortality. On average, 36,000 people in this
country die each year and 200,000 are hospitalized due to influenza and
influenza-related complications. Each year, influenza viruses undergo
small changes in their surface proteins as they circulate through the
human population. As these small changes accumulate, the influenza
virus gains the ability to overcome immunity created by prior exposure
to older circulating influenza viruses or by vaccination. This
phenomenon, called ``antigenic drift,'' is the basis for the well-
recognized patterns of influenza disease that occur every year, and is
the reason that influenza vaccines must be updated each year.
Influenza viruses can also change more dramatically; viruses may
emerge that can jump species from natural reservoirs such as wild ducks
to infect domestic poultry, farm animals, or humans. This type of
significant change in the antigenic makeup of the virus that infects
humans is referred to as ``antigenic shift.''
In most instances when influenza virus jumps species from an animal
such as a chicken to infect a human, the result is a ``dead end''
infection that cannot readily be transmitted further from human to
human. Mutations in the virus, however, could increase the efficiency
of human-to-human transmission. Furthermore, if an avian influenza
virus and another human influenza virus were to simultaneously co-
infect a person, the genes of the two viruses might reassort, resulting
in a virus that is readily transmissible between humans and against
which the population would have no natural immunity. In addition, the
reassortant virus could reflect the virulence of the avian virus. Such
a virus could potentially cause an influenza pandemic.
Historically, pandemic influenza is a proven threat. Three
influenza pandemics have occurred in the 20th century: in 1918, 1957,
and 1968. The 1918-1919 pandemic was by far the most severe, killing
approximately 500,000 people in the United States and 20-40 million
people worldwide--almost two percent of the global population at that
time. Worldwide, the pandemics that began in 1957 and 1968 killed
approximately 2 million and 700,000 people, respectively.
H9N2 and H5N1 influenza are two avian viruses that have jumped
directly from birds to humans and have significant pandemic potential.
In 1999 and 2003, H9N2 influenza caused illness in three people in Hong
Kong and in five individuals elsewhere in China, but the virus did not
spread from human to human. H5N1 influenza, often referred to as ``bird
flu,'' appears to be a significantly greater threat than H9N2. This
virus was first detected in humans in Hong Kong in 1997. Since January
2004, it has spread widely among wild and domestic birds and has
infected at least 97 people in Vietnam, Thailand, and Cambodia; 53 of
these people have died of the disease. Ominously, H5N1 viruses are
evolving in ways that increasingly favor the start of a pandemic,
including becoming more stable in the environment and expanding their
host species range. Moreover, there has been at least one highly
probable case of human-to-human transmission of the H5N1 virus, and it
is possible that other such transmissions have occurred recently.
The deadly experience with past influenza pandemics explains our
current high level of concern about the appearance of virulent H5N1
avian influenza viruses in Asia, which by a variety of mechanisms could
adapt themselves to efficiently spread from human to human and result
in the next pandemic. Given the poor condition of public health systems
in many underdeveloped regions and the speed of modern air travel, the
consequences of such an event, should it result in an influenza
pandemic, would be severe.
NIH INFLUENZA RESEARCH ACTIVITIES
Between influenza pandemics, when influenza activity occurs
regularly on a seasonal basis, the role of NIAID is to conduct basic
research into the viral biology, pathogenesis, and epidemiology of
influenza viruses and to study host immune responses to these agents.
Concomitant with these basic research studies, NIAID conducts applied
research to develop new or improved influenza vaccines and production
methods; to identify new anti-influenza drugs; and to support
surveillance for previously unknown influenza viruses in animals and
characterize any that are found. When a new influenza virus begins to
infect humans (and thereby gains the potential to cause a pandemic),
NIAID's role is to develop and clinically evaluate specific candidate
vaccines against the emergent strain, test the activity of antiviral
drugs, and, in some cases, supply vaccine manufacturers and the
research community with viral reference strains and other reagents to
speed vaccine development.
BASIC RESEARCH
NIAID supports many basic research projects intended to increase
our understanding of how influenza viruses replicate, interact with
their hosts, stimulate immune responses, and evolve into new strains.
Results from these studies lay the foundation for the design of new
antiviral drugs, diagnostics, and vaccines, and are applicable to
seasonal epidemic and pandemic strains alike.
NIAID also supports two special research programs to better
understand the diversity of influenza viruses. The Influenza Genome
Sequencing Project, launched in the fall of 2004, is a collaboration
between NIAID, the Centers for Disease Control and Prevention (CDC) and
several other organizations to determine the complete genetic sequences
of thousands of influenza virus isolates and to rapidly provide these
sequence data to the scientific community. This program will enable
scientists to better understand the emergence of influenza epidemics
and pandemics by observing how influenza viruses evolve as they spread
through the population and by matching viral genetic characteristics
with virulence, ease of transmissibility, and other properties. As of
May 24, 2005, 182 genomic sequences of influenza viruses had been made
available through this program to researchers via the NIH website, and
many more are in the pipeline.
NIAID also supports a long-standing program based in Hong Kong to
detect the emergence of influenza viruses with pandemic potential. This
program, led by Dr. Robert Webster of St. Jude Children's Research
Hospital in Memphis, Tennessee, conducts extensive surveillance of
influenza viruses in animals in Hong Kong, analyzes new influenza
viruses when they are found, and helps to generate candidate vaccines
against them. In January, the scope of this surveillance program was
expanded to include Vietnam, Thailand, and Indonesia.
Vaccines
Vaccines are essential tools for the control of influenza. NIAID
supports numerous research projects and other initiatives to foster the
development of new influenza vaccine candidates and manufacturing
methods that are simpler, more reliable, yield more broadly cross-
protective products, and provide alternatives to the egg-based
technology currently used to grow the vaccine viruses.
In the Fiscal Year 2006 budget request, DHHS has requested $120
million to support pandemic influenza preparedness activities. These
activities build on previous initiatives that include making chicken
eggs available year round to provide for a secure supply and surge
capacity for vaccine production and supporting efforts to shift vaccine
manufacture to new cell-culture technologies. Moreover, a technique
developed by NIAID-supported scientists called reverse genetics allows
scientists to manipulate the genomes of influenza viruses and to
transfer genes between viral strains. This technique allows the rapid
generation of vaccine candidate strains that precisely match a selected
epidemic strain. By removing or modifying certain virulence genes,
reverse genetics also can be used to convert highly pathogenic
influenza viruses into vaccine candidates that are safer for vaccine
manufacturers to handle. Other vaccine strategies for influenza,
including protein subunit and gene-based vaccines, are also being
actively pursued. On the NIH campus in Bethesda, the NIAID Vaccine
Research Center (VRC) has initiated a program to develop gene-based
vaccines against influenza. Should proof-of-concept studies prove
successful, the VRC expects to expand and accelerate the development of
gene-based and recombinant influenza vaccines.
In addition to supporting the development of new vaccine
strategies, NIAID maintains an extensive capacity for evaluating
candidate vaccines in clinical trials. For example, NIAID's Vaccine and
Treatment Evaluation Units (VTEUs) comprise a network of university-
based research medical centers across the United States that conduct
clinical trials to test candidate vaccines for many infectious
diseases. These units support both academic and industrial vaccine
evaluation, including safety, immunogenicity, and ultimately, efficacy
of candidate vaccines.
Although a pandemic alert has not yet been declared, NIAID has
taken a number of steps to develop and clinically test vaccines against
H5N1 and H9N2 influenza, two specific avian viruses that have
significant pandemic potential. For example, in August 2004, NIAID
contracted with Chiron Corporation for the production of 40,000 doses
of an inactivated H9N2 vaccine. A Phase I clinical trial of this
vaccine began on March 31, 2005, and is fully enrolled.
In January 2004, researchers at St. Jude Children's Research
Hospital obtained a clinical isolate of the highly virulent H5N1 virus
that was fatal to humans in Vietnam in late 2003 and early 2004 and
used reverse genetics to create an H5N1 candidate vaccine from this
strain. Immediately after NIAID received this vaccine last June, it was
sent to two companies, Sanofi-Pasteur (formerly Aventis-Pasteur) and
Chiron, which have NIAID contracts to manufacture pilot lots of eight
and ten thousand vaccine doses, respectively. The vaccines will be
tested in Phase I and II clinical trials that will assess safety and
the appropriate dose to optimize immunogenicity, as well as provide
information about how the immune system responds to this vaccine. The
Sanofi-Pasteur trial, which began on April 4, 2004, will test the
vaccine in approximately 450 healthy adults between the ages of 18 and
64. This trial is already fully enrolled and the safety data are being
analyzed. If data from this study indicate the vaccine is safe and able
to stimulate a certain immune response, NIAID expects to test the
vaccine in other populations, such as the elderly and children, in late
summer 2005. Trials of the Chiron-produced vaccines are expected to
begin later this year.
In addition to these relatively small pilot lots, DHHS contracted
with Sanofi-Pasteur to produce two million doses of its H5N1 vaccine,
in order to ensure that the manufacturing techniques, procedures, and
conditions that would be used for large-scale production will yield a
satisfactory product. Moving to large-scale production of the vaccine
in parallel with clinical testing of pilot lots is an indication of the
urgency with which we have determined that H5N1 vaccine development
must be addressed. Waiting for the results of the initial clinical
trials, which would be the normal procedure, would delay our ability to
make large quantities of vaccine by at least six months. These doses,
which have now been delivered, could be used to vaccinate health
workers, researchers, and, if indicated, the public in affected areas.
From the mid 1970s to the early 1990s, researchers in the NIAID
Laboratory of Infectious Diseases developed a cold-adapted, live
attenuated influenza vaccine strain that later became the FDA-licensed
influenza vaccine marketed as FluMist. Building on their experience
with attenuated influenza vaccines, researchers from the same
laboratory recently made three candidate attenuated H5N1 vaccine
strains and an attenuated H9N2 vaccine strain that are now in advanced
development. NIAID plans to start the clinical trial of the attenuated
H9N2 candidate vaccine this summer. These researchers also hope to test
one of the candidate attenuated H5N1 vaccines in a Phase I study this
year.
Antiviral Therapies
Antiviral medications are an important counterpart to vaccines as a
means of controlling influenza outbreaks, both to prevent illness after
exposure and to treat infection after it occurs. Four drugs are
currently available for the treatment of influenza, three of which are
also licensed for prevention of illness. NIAID actively supports
identification of new anti-influenza drugs through the screening of new
drug candidates in cell culture systems and in animal models. In the
past year, seven promising candidates have been identified. Efforts to
design drugs that precisely target viral proteins and inhibit their
functions also are under way. In addition, NIAID is developing novel,
broad-spectrum therapeutics that might work against many influenza
virus strains. Some of these target viral entry into human cells, while
others specifically attack and degrade the viral genome.
Efforts also are underway to test and improve antiviral drugs to
prevent or treat H5N1 influenza. Last year, researchers determined that
although H5N1 viruses are resistant to two older drugs--rimantadine and
amantadine--they are sensitive to a newer class of drugs called
neuraminidase inhibitors, including oseltamivir, which is marketed as
Tamiflu. DHHS has stockpiled approximately 2.3 million treatment
courses of oseltamivir, which is approved for use in individuals older
than one year. Scientists are planning to conduct studies to further
characterize the safety profile of oseltamivir in infants; and studies
are also in progress to evaluate novel drug targets, as well as long-
acting next-generation neuraminidase inhibitors. In addition,
development and testing in animals of a combination antiviral regimen
against H5N1 and other potential pandemic influenza strains are under
way.
CONCLUSION
In closing, Mr. Chairman, I would like to emphasize that although
we cannot be certain exactly when the next influenza pandemic will
occur, we can be virtually certain that one will occur and that the
resulting morbidity, mortality, and economic disruption will present
extraordinary challenges to public health authorities around the world.
We are working diligently in close coordination with our colleagues at
CDC, FDA, other federal agencies, and in industry to ensure that we can
meet these challenges in the most successful manner possible.
Thank you for this opportunity to appear before you today, and I
would be pleased to answer any questions you may have.
Mr. Deal. Thank you, Doctor. Dr. Gellin.
Mr. Gellin. Thank you. I want to join my colleagues in
thanking you for having this hearing.
Mr. Deal. Can you pull that one a little closer?
STATEMENT OF BRUCE G. GELLIN
Mr. Gellin. I want to thank you for holding this hearing
because it is something that you and we and all the Americans
really need to know about, as Ms. Baldwin mentioned. I am the
Director of the National Vaccine Program Office, which sits in
the Office of the Secretary of the Department of Health and
Human Services. And I want to join my colleagues here to thank
you for this.
As we have heard and you have been aware, the ecology of
the disease and the behavior of the virus changing now offers
multiple opportunities that could provide fertile ground for a
pandemic virus to emerge. And while we are all keeping a
watchful eye on the current situation in Asia, we recognize
that there are other strains of the influenza virus that could
perform similar tricks. And therefore, in addition to our focus
on this virus, we acknowledge that a pandemic could be
triggered by another influenza virus subtype and could
originate in any country.
Secretary Leavitt has made pandemic influenza preparedness
a priority area, and it is a critical component of his 500-day
plan for the department. As Dr. Gerberding mentioned, just last
week at the World Health Assembly in Geneva, the annual meeting
of the ministers of health from around the world, he emphasized
his concern about the situation in Asia and our department's
and our government's commitment to preparedness. He encouraged
global transparency, expanded surveillance, and timely sharing
of information and clinical specimens, the importance that all
nations have pandemic preparedness plans. He also urged
international collaboration among developed and developing
countries to control the spread of this virus and recognize the
important role of the human-animal interface.
On the home front last summer, as we have heard and will
discuss later, we released our draft plan last summer. The plan
described a coordinated strategy to prepare for and respond to
an influenza pandemic. It also provides guidance to State and
local health departments and the healthcare system to enhance
planning and preparedness at levels where the primary response
activities in the U.S. will be implemented.
When we posted our plan, we sought public input before
developing final guidance, and therefore allow the 60-day
comment period for that. In addition, the National Vaccine
Advisory Committee and CDC's Advisory Committee on Immunization
Practices are currently discussing with a number of
stakeholders to provide the department with recommendations on
some key policy issues that are outstanding.
As a complement to the plant, CDC is also finalizing a
series of specific guidance documents for State and local
health departments, communities, and the healthcare system. We
expect the updated plan and the related implementation guidance
documents will be available in the coming months, but also
recognize that plans like these will continue to evolve as we
learn more. Therefore, we expect that we will regularly and
continually review and revise the plan that incorporates new
research, changing influenza strains, the changing
epidemiology, lessons learned from the influenza season, and
other infections disease threats.
In addition, we also recognize the importance that all
Americans become aware of the threat of a pandemic and have
begun to engage a number of public engagement and education
projects because we seek the public's input into some of these
decisions that we are making as well.
Moving ahead with our preparedness isn't waiting for the
final drafting of the plan, as we have heard from both Dr.
Fauci and Dr. Gerberding. And given the central role that
vaccines play in preventing influenza, one of the critical
elements of our plan is to develop a strategy for sufficient
domestic surge capacity for vaccine production.
Our planning assumptions acknowledge that in a pandemic
emergency, there is likely to be worldwide demand for vaccine,
and vaccine produced outside the United States might not be
available for our use. One of the base assumptions that we have
in our planning is that the population has never be exposed to
a virus or anything like this, and therefore, all may be
susceptible, and therefore, all may need to be vaccinated.
And perhaps most importantly from a preparedness
perspective, because it is the nature of the virus to evolve
and re-assort with other influenza viruses, the perfect vaccine
cannot be prepared far in advance and stockpiled since that
vaccine is one that needs to be tailored to match the
circulating strain.
As Dr. Fauci has mentioned with his discussion of the NIH
clinical trials, HHS has developed a number of influenza
vaccine supply initiatives to address pandemic preparedness
needs, but will also be critical to achieving our annual
influenza prevention goal. The objectives of these initiatives
are to secure and expand U.S. influenza vaccine supply,
diversify our production methodology, and establish emergency
surge capacity. To support these activities HHS received $50
million in fiscal year 2004 and $99 million in fiscal year
2005. The 2006 budget includes an additional $120 million to
further strengthen this component of our overall pandemic
preparedness efforts.
To assure that vaccines can be produced at full
manufacturing capacity at any time of the year, we also need to
assure that we had an egg supply that could be available at any
time of the year. And last year HHS issued a contract with
sanofi pasteur that assures that they can manufacture influenza
vaccine at their full capacity all year long.
But diversifying influenza vaccine production methods will
also strengthen our system. As Dr. Fauci has mentioned, the
cell-culture technology is a well-established vaccine
production method for other vaccines and one that we hope can
be applied effectively to influenza vaccine production. This
technology does not require eggs as a substrate for growth and
therefore avoids some of the vulnerabilities that are
associated with that. And it also may be more amenable to surge
production for emergency vaccine production.
Because of this the secretary announced last month that the
Department of Health had issued a 5-year contract with sanofi
pasteur for $97.1 million to develop a cell culture vaccine.
The goal is to accelerate the efforts to bring such a vaccine
to the United States, that have the vaccine licensed by the
FDA, and to have it produced within the borders of the United
States.
These important steps to strengthen our influenza vaccine
supply, for assuring the egg supply, and diversifying our
expanding production capacity are to be followed this year by
additional measures to increase influenza vaccine capacity and
expand the number of vaccine doses and the number of
manufacturers that could supply vaccine to the United States.
Supported by the influenza vaccine initiative in the fiscal
year 2006 budget in our request for $120 million, our goals are
to build on our cell culture efforts and encourage additional
manufacturers to accelerate the development of cell culture
vaccines, to develop new vaccines such as recombinant vaccines,
to improve the efficiency of the existing manufacturing
processes, which could increase the overall yield of vaccines
and the amount produced, and to support research and
development of strategies that will stretch the number of doses
produced by decreasing the amount of virus antigen in each
dose, therefore making more vaccine from the same amount of
antigen.
Finally, I need to mention that coupled with the effort
that Dr. Fauci mentioned, last year we went ahead and had two
million doses of H5N1 vaccine produced, and we did in a time in
the fall that wouldn't interfere with seasonal production. We
wanted to make sure that a company was familiar with making
such a vaccine in full-scale facilities, and it was the first
project like this in the world. We are awaiting the results of
the clinical trials to know best how to use and formulate such
a vaccine.
We also recognize the important role of antiviral drugs in
stemming a pandemic. We have ordered and have already received
delivery of over two million doses of Tamiflu, and we are
currently in discussions with the manufacturer, Roche, who you
will hear from later today, to increase our national reserve of
this antiviral drug.
Stemming the spread of an epidemic will require close
coordination between agriculture and health sectors and among
effected countries, donor nations, and international
organizations. To that end we have a planning effort underway
to develop a plan for the $25 million that was included in the
fiscal year 2005 emergency supplemental to the Department of
State with the HHS focusing on health projects, and USAID, our
partner, focusing on projects on animal health.
Last week Dr. Gerberding and I were part of the U.S.
delegation accompanying Secretary Leavitt to the World Health
Assembly. Of the many discussions there, the one that best
captures the concern and common purpose that we all have is
summarized in Mr. Leavitt's remarks to his fellow ministers of
health: ``There is a time in the life of every problem when it
is big enough to see and small enough to solve. For pandemic
influenza preparedness, that time is now.'' Thank you.
[The prepared statement of Bruce G. Gellin follows:]
Prepared Statement of Bruce G. Gellin, Director, National Vaccine
Program Office, Office of Public Health and Science, Office of the
Assistant Secretary for Health, U.S. Department of Health and Human
Services
Mr. Chairman and Members of the Subcommittee, I am pleased to
appear before you today to discuss pandemic influenza and the measures
the Department of Health and Human Service is taking to prepare for the
next pandemic. As you may have heard from reports from last week's
World Health Assembly, many public health experts believe the threat of
a pandemic is now greater than it has been in decades. A report issued
by the World Health Organization warns that the virus may be evolving
in ways that increasingly favor the start of a pandemic. In addition
the ecology of the disease and behavior of the virus have changed and
are creating multiple opportunities for a pandemic virus to emerge.
This is in large part because of the bird flu that is established and
now endemic in many different species of birds across Asia. As these
bird viruses continue to evolve and spread in animals, the possibility
increases that an avian virus will mix with a human virus to cause a
novel and easily transmitted influenza strain in humans. Since 1997,
the avian flu has continued to evolve and has become increasingly
lethal for an expanding number of species, including mammals, not just
birds. Over the past year and a half, there have been 97 confirmed
human cases of influenza in Asia (Vietnam, Thailand and Cambodia) cause
by the H5N1 virus and over half of these people have died from their
infection.
Secretary Leavitt has made pandemic influenza a priority area. Just
last week, at the World Health Assembly--the annual meeting of
Ministers of Health from around the world--he emphasized his concern
about the situation in Asia and the Department's commitment to
preparedness. He encouraged global transparency, expanded surveillance,
and timely sharing of information and clinical specimens as part of our
global preparedness. Secretary Leavitt also urged international
collaboration among developed and developing countries to control the
spread of this virus among humans and animals. Further, the Assembly
considered a resolution on pandemic preparedness that was offered by
the U.S. as a blueprint for action.
In addition, on the national front, the Department has been
actively developing and formulating a Pandemic Influenza Preparedness
and Response Plan. This Plan describes a coordinated strategy to
prepare for and respond to an influenza pandemic. It also provides
guidance to state and local health departments and the health care
system to enhance planning and preparedness at the levels where the
primary response activities in the U.S. will be implemented.
This Plan was released for public comment last summer and, as with
all preparedness planning, the specifics of this plan will continue to
evolve. HHS will continually be revising and reworking the plan to
respond to events such as new research, changing influenza virus
strains, and discussions with the many stakeholders--state and local
health departments, the health care system, industry and the public.
Given the central role that vaccines play in preventing influenza,
one of the critical elements of this Plan is to develop a strategy for
sufficient domestic surge capacity for influenza vaccine production.
This will require an ongoing and sustained commitment by HHS.
Because a pandemic is by definition the introduction and spread of
an influenza virus to which humans have not previously been exposed,
this has major implications for vaccine development and supply. In the
setting of a pandemic, it is assumed that the pandemic virus will be a
novel strain. First, the majority of the population is likely to be
susceptible; immunologic naivety with the pandemic strain is likely to
result in the need for a two-dose regimen for effective immunity.
Unlike seasonal influenza epidemics, a pandemic could come at any time
during the year, and may last longer than a single season such that
booster dose(s) may be required to sustain immunity. Perhaps most
importantly from a preparedness perspective, the perfect vaccine cannot
be prepared far in advance and stockpiled, since the ideal vaccine is
one that should be tailored to match the circulating virus
Further, as highlighted by the SARS experience, modern
transportation and trade are likely to rapidly accelerate the global
spread of influenza. As a consequence, our planning assumptions
acknowledge that in a pandemic emergency, there will be worldwide
demand for vaccine and vaccine produced outside of the United States
may not be available for our use.
We are all keeping a watchful eye on the current situation in Asia
while at the same time recognizing that, in recent years, there have
also been outbreaks of avian influenza infections in Europe and in
Canada associated with human infections cases caused by other influenza
subtypes. Therefore, in addition to our concerns about the H5N1 virus
in Asia, we acknowledge that a pandemic could be caused by another
influenza virus subtype could originate in any country.
Though scientists in 1918 had very little idea of what was
happening until it was too late, we have time--and still have time--to
prepare for the next global pandemic, and we should consider ourselves
warned. As Secretary Leavitt stated at the World Health Assembly, ``We
are working on pandemic preparedness on borrowed time. When this event
occurs, our response has got to be immediate, comprehensive and
effective.''
I want to assure you that the Department has made this one of its
highest priorities and it is a critical component of the Secretary's
500-day plan. Ensuring the ability to meet current annual demand for
influenza vaccine, to improve the prevention of influenza disease, and
to prepare for an influenza pandemic all require strengthening the
influenza vaccine supply in the U.S. Building on the response to the
influenza vaccine shortage in the 2004-05 season NIH and FDA have
worked to facilitate the clinical evaluation in U.S. populations of an
influenza vaccine produced by GSK, and efforts are underway to
expeditiously consider a licensure application such that this influenza
vaccine may be licensed in the U.S. for the upcoming season.
Several HHS influenza vaccine supply initiatives have a longer
timeline and were developed to address pandemic preparedness needs but
which also will be critical to achieving annual influenza prevention
goals. The objectives of these initiatives are to secure and expand
U.S. influenza vaccine supply, diversify production methods, and
establish emergency surge capacity. To support these activities, HHS
received $50 million in FY2004 and $99 million in FY2005. The
President's Budget for FY2006 includes an additional $120 million to
further strengthen this component of the overall pandemic influenza
preparedness efforts.
Because influenza vaccine is produced to meet the seasonal demand
in the fall, production also is seasonal and embryonated eggs have not
been available to manufacturers year-round. Moreover, although some
excess supply of eggs may be available to support additional influenza
vaccine production or provide security if the flocks that produce eggs
for vaccine production are affected by avian influenza or other
illness, this excess is limited creating vulnerability to supply
disruption. To enhance influenza vaccine supply security, HHS issued a
five-year contract to Sanofi-Pasteur of Swiftwater, Pennsylvania, on
September 30, 2004 for $40.1 million. Under this contract, Sanofi-
Pasteur has begun to change its flock management strategy to provide a
secure, year-round supply of eggs suitable for influenza vaccine
production at full manufacturing capacity. It also will increase the
number of egg-laying flocks by 25% to provide contingency flocks in
case of an emergency. These eggs may be used to support additional
production of annual influenza vaccine in the event of a vaccine
shortage. Additionally, this contract provides for production of annual
investigational lots of prototype pandemic influenza vaccines, e.g.,
this summer, Sanofi-Pasteur will manufacture an H7N7 virus vaccine for
clinical evaluation.
Diversification of influenza vaccine production methods also will
help strengthen the system. Cell culture technology is a well-
established vaccine production method for other vaccines such as the
inactivated poliovirus vaccine and two companies have registered their
cell-culture based influenza vaccine technology in Europe. This
production technology does not require eggs as a substrate for growth
of vaccine virus, thereby avoiding the vulnerabilities associated with
an egg-based production system. It also may be more amenable to surge
capacity production when influenza vaccine supply needs to be expanded
rapidly such as at the time of a pandemic. Finally, influenza vaccines
produced in cell cultures rather than eggs will provide an option for
people who are allergic to eggs and therefore unable to receive the
currently licensed vaccines.
Secretary Leavitt announced last month that the Department of
Health and Human Services issued a five-year contract on March 31, 2005
to Sanofi-Pasteur for $97.1 million to develop cell culture influenza
vaccine technology and conduct clinical trials, with the goal of
obtaining an FDA license for this vaccine. Under this advanced
development contract, the company has also committed to manufacturing
this vaccine at a U.S.-based facility with a capacity to manufacture
300 million doses of monovalent pandemic vaccine over a one-year
period. However, given timelines for vaccine development and clinical
trials, and for construction and validation of manufacturing
facilities, additional influenza vaccine supply from this source is
unlikely to be available for at least five years.
These important steps to strengthen our national influenza vaccine
supply through assuring the egg-supply and diversifying and expanding
production capacity will be followed this year by additional measures
to increase influenza vaccine production capacity and expand the number
of influenza vaccine doses made using that capacity. Supported by the
pandemic influenza vaccine initiative in the FY 2006 budget request for
$120 M, we posted synopses of three additional areas where we believe
strategic investments move us toward achieving annual and pandemic
influenza vaccine supply goals in the March 17, 2005 edition of
FedBizOpps. On April 29, 2005, the first of these requests for
proposals was posted, providing support for the development of cell-
culture based and recombinant pandemic influenza vaccines.
Whereas building new influenza vaccine production facilities is one
approach to expand the influenza vaccine supply, other strategies also
can increase the number of influenza vaccine doses produced. Influenza
vaccine is manufactured in a series of steps--developing an influenza
virus master seed for vaccine production, inoculating the virus into
eggs, growing, harvesting, purifying, splitting, formulating, and
filling it into vials or syringes. Improving efficiency at any step in
this process can increase the eventual yield and number of vaccine
doses produced. Thus, a second area of emphasis will be to support
improvements of the manufacturing process to increase overall influenza
vaccine production at current manufacturing facilities.
The third area of emphasis will provide support for research and
development, leading to licensure of strategies that will stretch the
number of vaccine doses produced by decreasing the amount of influenza
virus antigen that is needed in each dose. The concept underlying these
``dose-stretching'' strategies is that by changing either the influenza
vaccine or the way its administered, one can improve the immune
response to vaccination and provide protection while using less of the
vaccine antigen. By using less antigen in each vaccine dose, the number
of doses that can be made at any level of production capacity can be
multiplied. The two most promising antigen-sparing approaches are
either to add an adjuvant--a substance that stimulates the immune
response to a vaccine formulation, or administering the vaccine into
the skin (similar to the approach used in a skin test for Tb) where
large numbers of potent immune cells are located. Both strategies have
been evaluated in several clinical trials and have the potential to
expand influenza vaccine supply several-fold if they prove effective in
further clinical trials and are approved for licensure.
The increases in the FY 2006 President's Budget request will
support ongoing activities to ensure that the Nation will have an
adequate influenza vaccine supply to respond better to yearly epidemics
and to influenza pandemics. While issuing the requests for proposals
and completing the contracts is only the first step toward the
development of an expanded, diversified, and strengthened influenza
vaccine supply, the U.S. is leading the global effort to develop
vaccines and vaccine technologies to meet this challenge.
We also recognize the important role of antiviral drugs in stemming
a pandemic and for treating patients. The United States has ordered and
received delivery of 2.3 million treatment courses of Tamiflu. We are
in discussions with Roche, the maker of Tamiflu ', to
increase our national reserve of this antiviral. Unfortunately, the
H5N1 virus is resistant to the adamantine drugs, the only other class
of anti-influenza drugs.
Stemming the spread of the epidemic will require close coordination
between the agriculture and health sectors and among affected
countries, donor nations and international organizations dedicated to
promoting the health of humans, livestock and wildlife. Detailed joint
planning is already underway to develop the proposed budget plan for
the $25 million that was included in the FY 2005 emergency supplemental
with the Department of State with HHS focusing on human health projects
and USAID focusing on projects on animal health and related issues. In
this way, the two agencies' plans will be complementary, not
duplicative.
I was part of the U.S. delegation that attended last week's World
Health Assembly and want you to know that this administration and the
global health community are working together on this public health
threat in anticipation of the next pandemic, be it tomorrow or ten
years from now. As Secretary Leavitt told the assembled in Geneva,
``There is a time in the life of every problem when it is big enough to
see and small enough to solve. For pandemic influenza preparedness,
that time is now.''
Thank you for your attention to my remarks this morning--and more
importantly to the attention that you are paying to this important
global public health issue.
I would be happy to answer any questions from the Committee.
Mr. Deal. Thank you. I recognize myself for some opening
questions. It appears that we are now sort of focusing on the
H5N1 as the flu that we think might be the one most likely to
occur in pandemic form. Suppose we are wrong and it is the H9.
Will vaccines that are developed for the H5 be effective for
H9? Let me go ahead and ask a few series of questions and then
I will let whoever wants to respond. That is the first question
I have.
Second, are there antivirals that are being developed for
this H5N1 or are antivirals somewhat generic in nature? Can
they be used for any variation of strains or must they likewise
be specific to the strain that we are facing?
The last two questions are is HHS contemplating stockpiling
injection devices that would be needed in the event of a
pandemic?
And last, I understand that there were some conditions in
trying to trace the SARS issue that CDC faced in terms of being
able to obtain passenger contact information. Have we overcome
those administrative difficulties so that HHS or any other
Federal agency would be able to provide the information
necessary to trace someone who potentially has the H5 or any
other variation of that virus coming into our country? I know
that is a lot of questions and I will let you start.
Mr. Gellin. Well, actually, you have a question for each of
us.
Mr. Deal. Okay.
Mr. Gellin. Let me attack the vaccine and antiviral
development one. You ask a very good question. The short answer
to the question if you have an H5N1 vaccine, and, for example,
an H9N2 virus circulating, the degree of protection would be
minimal if none at all. So that is a clear answer to that
question. I would point out in relationship to that question
that for that very reason we are not just doing the trial with
an H5N1. We have already started an H9N2 trial in much the same
philosophy of looking at safety and proper doses of the H9N2.
Having said all that, if it is something else that is not
H9N2 or not H5N1, the very fact of getting more experience with
how the body responds to an antigen like an H5 or an H9 to
which there have not been previous exposure will give us a lot
of important information to more rapidly respond to whatever
evolving Bird Flu, whatever the subtype is. So that is the
answer to the question, but it also--the two million doses of
the H5N1 allowed us to be able to make this kind of a vaccine
in scale-up quality. So even though we are doing things now
that might not be precisely matched to the ultimate pandemic
flu virus, everything we are doing is going to helpful for
that.
With regard to the antivirals, Tamiflu is the antiviral to
which H5N1 is sensitive. The issue of developing antiviruses
that have a broad range of capability is part of the research
plan, as is developing vaccines that have broader capability,
not to be only effective against one but against another. That
is something that is difficult scientifically to do, but it is
very high on our research agenda to do that.
And finally, with regard to the antiviral ability to block
the influenza, we have to be very careful that there is not a
perception that this is like an antibiotic that you treat
pneumonia. You give it and the pneumonia is gone. This will
maybe decrease some of the days of illness and be very, very
useful, but we don't want you to get the impression that this
is a knockout drop for the virus. It is not. And we have other
questions that Dr. Gerberding will be able----
Ms. Gerberding. The question about syringes is one that is
easy to answer. We have a supply of a lot of medical equipment
in the stockpile, and we are not concerned about shortages of
syringes limiting immunization. The exact contents of the
entire medical stockpile is something that we consider
sensitive, so we would be happy to discuss with you in chambers
the very specific contents of the stockpile.
And with respect to the issues around contacting
passengers, our Division of Global Migration and Quarantine has
been working with leaders at HHS and the administration to come
up with some policies and procedures that would improve that
process. Right now we are engaged in a pilot project with one
major international airline to see if the data systems protect
the confidentiality of the passengers but do allow this kind of
reconnection. And we have already had one, I think, small event
where it has been tested. It looks very promising. So we are
taking an evidence-based approach to this. Find out a) does it
work, b) is it acceptable to passengers, and c) can we do it at
a cost that makes it a worthwhile investment. And we will know
more about that probably later this year.
Mr. Deal. Thank you. Mr. Brown.
Mr. Brown. Thank you, Mr. Chairman. Dr. Gerberding, GO
testified that insufficient hospital and health workforce
capacity is a substantial area of concern. If you would, share
with us your characterization of the adequacy of our hospital
and health workforce capacity to deal with a potential
pandemic, and if you think there are gaps, would you point us
to specific provisions in the fiscal 2006 budget that are aimed
at addressing these gaps?
Ms. Gerberding. I will do my best to address that, and I
may have to call upon Dr. Gellin to add perspective from the
other agency that is involved in that, which is HRSA. I think
we appreciate that our entire healthcare system lacks surge
capacity for any kind of a major health issue. Workforce
retention, development, recruitment, and training are issues
that we all have a generic concern about. Since the terrorism
preparedness investments have been made by HHS, we have been
able to target some specific preparedness activities to support
surge capacity, and this year proposed in the stockpile funding
is money for portable hospital facilities of a variety of
levels of care so that we could bring portable facilities to a
site of a major event. And I will ask Mr. Gellin to add any
information from the HRSA perspective.
Mr. Gellin. I think I will defer that and provide you that
information in writing from HRSA so we are precise about it.
Mr. Brown. Okay. Could you fill us in on your discussions
with the administration and their responses when you talk about
the gaps or the inadequacies of public health structure's
ability to deal with a pandemic outbreak?
Ms. Gerberding. I can summarize all of this by saying I
think Secretary Leavitt represents the administrative position
very well and the high priority he has put on this, as well as
the investments that are proposed in the President's 2006
budget to increase the Vaccines for Children Program, increase
the purchase of vaccines in the 317 Program to allow CDC to buy
a backfill--sort of an insurance policy by buying bulk
monovalent and vaccine in worst-case scenario, to increase the
ability of the States to purchase vaccine, as well as to change
the Vaccines for Children Program to increase access for
underinsured children to receive vaccines. So all of these are
plus ups in the budget.
I just mention that this year CDC's influenza budget is
$197 million, and that is about a log larger than it was just a
few years ago. So we are seeing proposed investments that I
think augment and buildupon the investments that we are making
for terrorism preparedness in the States. The capacities, as
you know, are part and parcel of the same--detection,
surveillance, investigation, communication, informatics, and
alerting. So it is my experience that the entire department, as
well as the rest of the administration, is engaged in influenza
and working very hard to come up with a cogent approach that
would serve as well and to do it as fast as we can.
Mr. Brown. You argue or suggest that support from our
government is adequate--from Congress, appropriations are
adequate, perhaps, for what you do specifically at CDC on that
level. What do you see when you look at hospitals and hospital
infrastructure and its abilities? Do you see funding gaps there
and funding problems there? Or do you see an adequate amount of
resources that they are getting from State and local and
Federal Governments?
Ms. Gerberding. I am concerned, but I don't have data to
answer your question. Again, this is a part of HRSA
responsibility that we can provide you a factual representation
of the degree of support and where the gaps might lie.
Mr. Brown. Do the other two of you want to comment on that
or just simply something written? Okay. Thank you, Mr.
Chairman.
Mr. Deal. Thank you. Mr. Ferguson.
Mr. Ferguson. Thank you, Mr. Chairman. Dr. Gerberding, I am
interested that in your statement or just your comments this
morning that you didn't talk about antivirals really. You were
talking about vaccines. But can you talk a little about the
role that antivirals will play in an Avian Flu outbreak and in
any kind of a pandemic flu outbreak?
Ms. Gerberding. I think it is important to distinguish the
H5N1 situation that we are looking at right now in Asia with
the realm of possible influenza outbreaks that may occur. This
particular virus strain happens to be resistant to the
inexpensive, easily produced drugs. So if our only goal was to
protect against this specific strain, stockpiling the other
drugs doesn't make sense. But there are many other strains of
flu that are susceptible to the inexpensive drugs. So we have
made the decision to stockpile both categories of drugs. We are
emphasizing oseltamivir right now because it is the drug most
likely to be useful if this particular strain breaks. But we
also have a stockpile of about four million treatment courses
of rimantadine, which could be used for seasonal flu of a
susceptible nature, or even an Avian strain that proved to be
susceptible.
The problem with this antiviral stockpiling and capability
can be summarized in the phrase ``lack of evidence.'' We know
that antiviral drugs, as Dr. Fauci said, can reduce the
severity of illness as characterized by days of hospitalization
and can benefit people if they are taken within 2 days of the
onset of illness, which is very, very hard to do. You know,
when you start getting the flu it is hard to distinguish it
from any other upper respiratory infection, so most people
don't realize they have flu until it is past the 48-hour
window.
But in addition, we do not have evidence that even
oseltamivir actually reduces mortality from influenza. The
studies simply haven't been done. We are concerned at some of
the things we are seeing in Vietnam where some patients who
apparently were started early on the drug have not done well
and have gone on to die despite treatment. So we need the
scientific evidence to tell us how should the drug be used?
Does it actually reduce mortality? What is its role in a
pandemic? We are working with WHO and others in the department,
including the FDA. We have been having regular conversations on
how we might be able to conduct such trials in a situation
where cases right now are still sporadic.
But until we actually know how to use the drugs, making
enormous purchases in stockpiling may be a premature decision.
And that is why we are scaling up our purchase as we feel we
can define an effective role, but we have more work to do to
really look at all the information and make the best possible
long-term decision.
One other point I should make is that this right now is an
oral drug. It is taken by mouth. And some of the patients with
severe influenza in Asia have an illness that is not just
respiratory in nature. It involves the GI tract and all other
organs, and so we have to be concerned could this drug even get
absorbed from the intestinal tract if people are ill with
influenza. So we have a lot of work to do to be able to define
the appropriate role for saving lives during flu and that work
needs to be a high priority.
Mr. Ferguson. But clearly our government is placing some
new importance on the role of antiviral. We are going to hear
more about antivirals in our next----
Ms. Gerberding. Absolutely.
Mr. Ferguson. [continuing] panel.
Ms. Gerberding. Absolutely.
Mr. Ferguson. And we are beginning to order millions and
millions of doses I am told by some of the companies. To me it
highlights that there is an increased awareness and
appreciation for the role that antivirals can play.
Ms. Gerberding. Yes, we have a stockpile right now of more
than two million treatment courses of the oseltamivir, and with
the supplemental appropriation we just received through the
defense funding, the $58 million will be looking at what we
might do with that resource to augment our stockpile also.
Mr. Ferguson. I am sure you would agree with me that two
million doses is a pittance. I mean that is nothing compared to
what we would need were we to have some sort of a pandemic flu
outbreak. But let me just--because my time is running short. I
mean I think last year's vaccine shortage highlighted the
question of the distribution--partnership that is going to be
necessary, and even if we are stockpiling vaccines, stockpiling
antivirals, what kind of a plan is in place and who is
ultimately responsible for making sure the plan works to make
sure that--I mean it could be because you are talking--I think
the necessity of a 2-day window for someone to take an
antiviral if they are showing signs of a flu, that I think
highlights to me the necessity of having a distribution plan in
place where these products are available and around the
country. They are not all kind of sitting in one storehouse
somewhere in one city or one part of the country that that--I
mean it highlights to me that we need to have a real
distribution plan in place. Can you shed some light on that?
Ms. Gerberding. Any doctor can prescribe oseltamivir today,
and it is available. We inventoried during last flu season. It
is available in most pharmacies and could be readily available
up to the amount that the manufacturer produces. So right now
the commercial distribution system does a very good job of
covering the United States. If we have stockpile drug and we
need to allocate it in a setting of a flu pandemic, we would
have some time to do that. We wouldn't expect instantaneously
everyone in the country to be ill at the same time. So we would
be able to distribute drugs in collaboration with the State
health departments and others who have that primary
responsibility depending on where the need was the greatest.
But that is part of the reason why we would like to have a
larger stockpile, because the more pre-deployment we have in
the system, the easier it is to handle that when people are
frightened and upset.
I should also say that we are evaluating a number of
options to support or augment distribution, including options
that have been explored for terrorism events where
countermeasures have to be delivered very quickly. One of those
mechanisms involves working with the U.S. Postal Service to
deliver products to people's homes. Another option might even
include the idea of having the drugs forward-deployed at the
community level or even the household level. So these are all
things that are on the table right now, and we are working with
experts inside and outside of government to come up with some
evidence and some protocols to see which really will be the
best approach.
Mr. Ferguson. Mr. Chairman, I know my time is up, but just
for me to close, I think it is important that we not
underestimate the importance of antivirals in this process. And
some of your comments suggest that perhaps you don't have the
same appreciation that I might have or some folks at the World
Health Organization. Their recommendation has been that, you
know, countries have the ability to treat 25 to 50 percent of
their population with antivirals. If we are talking about two
million--even if we were talking about 50 million doses, that
would not be enough. That would not be meeting the World Health
Organization's recommendation so----
Ms. Gerberding. But let----
Mr. Ferguson. [continuing] I would urge you to look closer
at some of those recommendations and perhaps take them to
heart.
Ms. Gerberding. Let me just be very clear. We do support
stockpiling antivirals; we do think they have a role. We have
defined the role of antivirals right now as one for treating
affected people, and in certain situations, as a preventative
for mission-critical personnel. We know the drug is effective
at preventing seasonal flu, but obviously no one can treat the
entire world with oseltamivir during the many, many months of a
pandemic. So prophylaxis for the population is not sensible.
But I also wanted to emphasize, even those who are making
projections about the proportion of population that should be
covered are not doing that from a data base perspective or
for--in some cases even credible models of how the drug would
be used and distributed. So we have a lot of work to do to
create a frame and a plan that includes antivirals in the
context of other measures that must play a role, including
isolation of cases and quarantine of exposed people.
Mr. Ferguson. Thank you, Mr. Chairman.
Mr. Deal. Thank you. As you know from the bells, we have a
vote that is going on on the floor, and I want to commend the
audience; I don't think I have heard a cough yet. We will
resume as soon as these votes are concluded, and there are a
series of votes, so we will be gone--yes.
Ms. Eshoo. If I could just ask my question, and I think I
am next because I have another hearing of----
Mr. Deal. Can you do it quickly?
Ms. Eshoo. I can do it very quickly.
Mr. Deal. Okay.
Ms. Eshoo. To Dr. Gerberding, the GAO requested a plan, as
I understand it, in 2000. And what I heard you say in your
opening statement is that even though there has been a
temporary report that has been issues, that you are just going
to move ahead without doing a final report? I mean, I think
that there is a little bit of a--I sense a conflict between
what we need, what has been requested, a temporary report, all
the needs that have been stated today, and how these conflicts
or the differences or the gaps between a temporary report and a
final report to the Congress, I am concerned about that because
it really comes under the umbrella of a plan for our country.
So you can either respond now or respond in writing.
And, Dr. Fauci, your testimony today, again, represents a
great deal of hope, very exciting research and I think that it
is good news for our country and that we are moving ahead. So
if you----
Ms. Gerberding. I would like to answer----
Ms. Eshoo. [continuing] address yourself----
Ms. Gerberding. [continuing] your question quickly----
Ms. Eshoo. [continuing] to this because I am concerned
about the, you know, the stated commitment but the lack of a
plan and a timeframe for it.
Ms. Gerberding. I think it is very important to understand
how preparedness works. A plan would not necessarily be a good
idea because look at all of the things that have happened in
the last----
Ms. Eshoo. Well, why----
Ms. Gerberding. [continuing] year----
Ms. Eshoo. [continuing] wasn't that stated when the GAO
requested one?
Ms. Gerberding. Well, I am not sure what the GAO is
thinking, but we are intent on having a framework so that we
can continuously update and improve. And I will ask Dr. Gellin
because this plan right now is in his hands. And we are very
intent on getting the stakeholders who have to execute the
plan----
Ms. Eshoo. So there is a----
Ms. Gerberding. [continuing] to have a voice in that
process.
Ms. Eshoo. [continuing] temporary plan now and you are
moving toward a final plan? And is that----
Ms. Gerberding. There are elements of the plan that we
already all agree on, and we are acting on those elements.
There----
Ms. Eshoo. Will there be----
Ms. Gerberding. [continuing] are some elements----
Ms. Eshoo. [continuing] a final plan?
Ms. Gerberding. [continuing] that still have to be worked
out. One of them----
Ms. Eshoo. Will there be a final plan----
Ms. Gerberding. [continuing] was mentioned----
Ms. Eshoo. --Dr. Gellin, which will then be brought back
and reported to the Congress, and if so, when?
Mr. Gellin. Well, there will be a final plan in the sense
that these plans are evergreen and that we know that they will
continue to be revised. That said, I think the distinction
between the moving ahead versus the final plan is more of how
we are addressing the pandemic threats. You have heard from Dr.
Gerberding and Dr. Fauci many of the specifics going into
things that we are doing now because we are so concerned about
the threat of the H5N1 virus and the bubbling up of other
viruses around the world.
But the plan itself, as I mentioned, was lacking a few key
policy decisions, but we put it out for public comment and we
were seeking the input from others because we felt this was so
important and it could affect every American, we wanted
everyone potentially engaged in that. So while a large part of
that framework is completed, some of those components, the
distribution and control of vaccines, as we were just talking
about----
Ms. Eshoo. But do you have a plan for a final plan? When do
you anticipate----
Mr. Gellin. Plan for----
Ms. Eshoo. [continuing] bringing back----
Mr. Gellin. This summer.
Ms. Eshoo. [continuing] something that is----
Mr. Gellin. This summer.
Ms. Eshoo. [continuing] rounded out----
Mr. Gellin. As I mentioned there are a number----
Ms. Eshoo. [continuing] but perhaps to this committee----
Mr. Gellin. Sure.
Ms. Eshoo. [continuing] which has jurisdiction.
Mr. Gellin. Well, we would be happy--we will post it for
the world on our website and we will share with the World
Health Organization when it is available. We would be glad to
come and talk to you about it as well. We expect it will be
completed----
Ms. Eshoo. Do you anticipate approximately----
Mr. Gellin. This summer.
Ms. Eshoo. [continuing] when?
Mr. Gellin. This summer.
Ms. Eshoo. I mean is it 2 years from now or a year----
Mr. Gellin. This summer.
Ms. Eshoo. This summer?
Mr. Gellin. This summer. As I said, there are a number of
moving parts that are going to funnel into it, and we are
hopeful that they are all going to be completed. The CDC is
working on some, various advisory committees are working on
them, and they are all anticipated to funnel in to fill the few
gaps that were in the plan from last year this summer.
Ms. Eshoo. Thank you. Thank you, Mr. Chairman.
Mr. Deal. Thank you. The committee stands in recess.
[Brief recess]
Mr. Deal. The subcommittee will come back to order. I
recognize Dr. Burgess for questions.
Mr. Burgess. Thank you, Mr. Chairman. Dr. Gellin, on the
issue of liability that inevitably comes up in a discussion
like this, have you got any thoughts on the issue of liability
and protection from liability that may enter into this
discussion?
Mr. Gellin. Well, specifically for this discussion, I think
it is worth highlighting that the National Vaccine Injury
Compensation Program that added the influenza vaccine to their
compensation table this year added a trivalent vaccine, the
current annual vaccine of three strains. And I believe that
probably gives us some indication that a pandemic vaccine,
which we all believe would likely be a monovalent strain of the
pandemic strain wouldn't be covered by the compensation
program. In my reading of the history of the Swine Flu epidemic
in 1976, the manufacturers--I believe, and they will probably
tell you about that--but produced vaccine but wouldn't release
it until the liability question was solved. I think among the
pieces of the preparedness plan, at least that have been
highlighted as one that needs to be solved, is the one that is
being worked on, but clearly needs to be solved before we can
move forward. And a large response is that issue.
Mr. Burgess. Thank you. And, Dr. Gellin, the vaccine
shortage from last year, the utilization of information,
lessons learned from that vaccine shortage, has that in any way
helped us nationally plan for the pandemic flu response?
Mr. Gellin. Absolutely. And I think that what your question
really highlights is really the inseparable link between our
annual influenza program and our preparedness for a pandemic.
And that speaks probably to every component of that from
communications to vaccine distribution to vaccine availability.
So we learned many lessons last year. And I think that one of
the other questions that needs to be addressed and is one of
those key policy decisions that was intentionally left out of
the plan because we wanted a larger discussion was the
procurement and distribution and essentially the control of
vaccine in a pandemic.
It is worth highlighting that while we all think about flu
shots and public health and therefore you think that this must
be a public commodity, 85 percent, I believe, of the flu shots
that are distributed annually are in the private sector. And I
think that what we saw some last year is that the control of
vaccine was really an impairment to the distribution of
vaccine. Therefore, I think we need a vigorous discussion that
goes into our policy decisions about procurement and control of
a pandemic vaccine.
Mr. Burgess. Thank you. Dr. Gerberding, Dr. Fauci talked
about fast science and how good we are now at identifying
things. The concept of syndromic surveillances is something
that comes up from time to time. Are we making any effort to
tie into any of the large drugstore chains to see when the
sales of Kleenex and aspirin spike so that we could even be a
little bit faster about trying to identify these outbreaks?
Ms. Gerberding. Thank you. During this past flu season we
did test out our system called BioSense, which allows us to
import information from pharmacies as well as clinical visits
in the VA and the Department of Defense sites across the
country, of course, anonymously without revealing patient
identifiers and a number of other related, surrogate health
data short of actual patient visits to the hospital or
clinician for influenza. And what we found was that our
inputted information from over-the-counter purchases of flu-
type medications in conjunction with clinic visits in the
Department of Defense and VA medical facilities allowed us in
some jurisdictions to see the arrival of flu earlier than our
conventional surveillance and with more precision at the local
level than our conventional surveillance. For seasonal flu that
is probably not particularly helpful to the public health and
the doctors making the decisions, but in the case of something
like exotic Avian Influenza or pandemic strain or SARS, the
sooner we know that at the most local level, the sooner we can
initiate isolation, quarantine, and other control measures. So
we think this is definitely an investment that has proved its
use, and we continue to evaluate it and improve it over the
next year. So we actually appreciate the support that Congress
has given us for the BioSense initiative.
Mr. Burgess. Well, and also, of course, most of the agents
that are discussed as far as Homeland Security, the
bioterrorism agents would present with the same symptoms as an
influenza outbreak?
Ms. Gerberding. That is correct. There is always a dual
purpose. Everything we do with flu helps us with terrorism
preparedness and vice versa.
Mr. Burgess. I guess, Dr. Gellin, Mr. Brown asked you about
surge capacity in the provider market, and has there been any
thought given to--you know, there are physicians out there who
are licensed and capable but no longer insured because they
might be retired, serving in Congress, any number of other
occupations. And has there been any thought given to a limited
liability protection during a crisis that would provide some of
that surge capacity that you say we lack?
Mr. Gellin. Well, I can't speak to that, but specifically
for a pandemic response I don't know if that has been addressed
in bioterrorism, but clearly we recognize that the kinds of
numbers that you all have been aware of and have discussed with
us, it would rapidly overwhelm the healthcare system and need
to try to think of alternative levels of care and what it would
take to allow that to happen.
Mr. Burgess. Thank you. This has been a fascinating
discussion this morning. I hope I can get continuing education
hours. Thank you, Mr. Chairman.
Mr. Deal. The gentleman from California, Mr. Waxman.
Mr. Waxman. My colleague wants not only continuing
education but a legal liability protection if he is called into
service. Not unreasonable. Not unreasonable at all. Dr.
Gerberding, we are going to hear on the next panel from sanofi-
aventis, the only company with a plant licensed to produce flu
vaccine in the United States, and they also make several
childhood vaccines, including vaccines to prevent polio,
tetanus, and whooping cough. And the company is going to tell
us that in the event of a pandemic, virtually all of their
efforts would be directed toward a flu vaccine and production
of other vaccines would plummet. Now, that might not be a
problem if we have a stockpile of all the pediatric vaccines.
Three years ago CDC pledged to fill this stockpile, but as the
``Washington Post'' recently reported, very little progress has
been made. Over 2 years ago sanofi-aventis raised the concern
with CDC that an obscure accounting rule of the Securities and
Exchange Commission was an obstacle to participation. The SEC
issue has since been discussed in advisory committee meetings
and CDC presentations and scholarly publications, yet for all
this talk, very little action. And I just learned that 2 days
ago, the SEC sent its first letter to the vaccine companies
asking for more information. The SEC is hoping the companies
will call by June 7 in order to schedule a conference call or a
meeting.
Now, if CDC was aware of the problem 2 years ago, why does
it seem to be stuck at square one in May 2005, and what are you
doing to express the urgency of this situation to Secretary
Leavitt at HHS and Chairman Donaldson at SEC? When do you
foresee this problem will be resolved? When can we expect the
stockpile to be filled? This is not a complicated problem. We
need vaccines for a stockpile so that we can protect children's
lives. But the stockpile is now virtually empty and children
are at risk, and if a high enough priority is placed on
children's health by this administration, this problem should
be able to be resolved I would think immediately. I know it is
not your problem alone, but it is others' within the
administration. When are we going to see action on this?
Ms. Gerberding. This is a frustrating situation. For 20
years we have been purchasing drugs for the pediatric supply
using a method that served us very well, and suddenly a couple
of years ago, as you mentioned, the accounting rule was noticed
or interpreted differently than it had in the past, and some
companies are concerned enough to no longer want to stockpile
drugs and vaccines using the old methodology.
We had a very difficult time getting an accountant with
objectivity to help us because most of the accountants that we
approached for contractual relationships have conflicts of
interest because they also do work for PhRMA. So the process of
getting the external advice and help that we needed took longer
than you can imagine. It was a very frustrating situation, but
the accountant is on board. We do have an objective accountant
that I think we would all agree does not have a conflict of
interest in how to arbitrate and negotiate a decision.
I will be frank with you; I am not an expert in Securities
and Exchange law, but I know that Secretary Leavitt and the
department have been working hard to try to find some
alternative strategy. The reason that we have managed the
stockpile in this way is because we don't want to purchase
vaccine and have it expire and not use it----
Mr. Waxman. No, I understand that and----
Ms. Gerberding. [continuing] so it is----
Mr. Waxman. [continuing] it must be----
Ms. Gerberding. The solution is expensive----
Mr. Waxman. Yes.
Ms. Gerberding. [continuing] and we are looking----
Mr. Waxman. Well, it must be----
Ms. Gerberding. Isn't there some----
Mr. Waxman. [continuing] frustrating to you----
Ms. Gerberding. [continuing] third way----
Mr. Waxman. [continuing] and it is frustrating to everybody
involved. One person suggesting putting people in the room and
not letting them out until they have resolved it. I want to
express to you on my behalf, and maybe I speak for other
members as well, if you need a special exemption in the law on
this one issue in order to give comfort to the companies to
produce the stockpile, if that is what it comes to, I would
certainly support such an effort. So I just want to encourage
you to push the secretary, who has so many other things on his
mind, to not forget this one because it could blow up in our
face.
The key Federal program that supports State immunization
activities is the 317 Program. It supports basic childhood
immunization as well as resources and training directly related
to pandemic flu preparedness, and for years States have raised
concerns about Federal support. They say 317 is inadequate.
Spending for vaccine planning staff has remained flat even
though costs have risen. More than 15 States say they don't
have the resources to provide routinely recommended vaccines
such as a vaccine against the most common cause of meningitis
to all children who need it.
Last year Congress provided an extra $6 million for the 317
Program, but then that money had to be diverted when we had the
flu crisis. States have said they are not seeing the increase
in funding even though they were told they would get it. Is
this extra funding going for vaccine purchase, and if not,
where it is going? I assume that is where it is going. Last
fall CDC took money from the 317 Program to purchase flu
vaccine. Has all the funding been restored to the 317 Program?
Can you pledge that it will be fully restored?
Ms. Gerberding. No, let me first say that use of 317 money
for the IND vaccine has been fully restored, so we did not
borrow from 317 on a permanent basis to pay for the vaccine. We
reprogrammed through Congressional action to pay for those
expenses through non-317 dollars. And overall there is a net
increase in 317 support. I would also mention that we have
record high immunization records of children across our Nation.
So whatever difficulties the States are having, they have been
able to get the best-ever vaccination rates in very difficult
times, which I think is a testament to their incredible
innovation and creativity under some pretty high pressure
circumstances.
Mr. Waxman. So it is your position that there really has
not been a decline in 317 funds? The money has been restored
and it is available?
Ms. Gerberding. There is an actual, absolute increase in
the funding for 317. But the other part of this that hasn't
been resolved yet is the change in the Vaccine for Children
Program that would allow a population of children that right
now experience a coverage gap. Uninsured children in the
country cannot get vaccine through the 317 Program in the
locations where we would like them to be able to access it. And
we are supporting a change in vaccines for children that would
cover those children under the mandatory vaccination program so
they would no longer be relying on 317 funds. That should help
improve coverage.
Mr. Waxman. Thanks. Well, it is an important program, and I
just want to urge you to make sure that we have enough funds in
there for the States to do their job.
Ms. Gerberding. Thank you.
Mr. Waxman. Thank you. Thank you, Mr. Chairman.
Mr. Ferguson [presiding]. As we are waiting for members of
the majority side to come back we will go to Mr. Allen.
Mr. Allen. Thank you, Mr. Chairman. This is a question for
the whole panel really. I am just wondering what your estimate
is of the time it would take between identification of a
pandemic strain and full-scale production of a vaccine against
that strain? I know some assumption is built in there, but I
wondered if you could give us your thoughts on that question.
Ms. Gerberding. We face a similar situation every year
because we see season flu emerge at the end of the regular flu
season, and we have got to scale everything up to be able to
produce the next vaccine for the fall. So 6 months is the best
we can do right now under our current manufacturing processes.
And part of the reason that the vaccine, the H5 vaccine, the
two million doses is so important is because some of the
regulatory steps to allow for good manufacturing practice
approval, those hurdles have already been solved. And if we
have to suddenly use the slightly different H5 strain or scale
up the production of this one, we have cutoff a little bit of
the regulatory barrier to the time. But egg production takes
time. It takes time to get a seed virus and it takes time to
grow it in eggs; it takes time to harvest it; it takes time to
package it and test it and then distribute it. So we would have
to count on a 6-month window before we would have full-scale
global production.
Mr. Fauci. Yes, I agree completely with Dr. Gerberding's
estimate of the timeframe, Mr. Allen, but I would like to take
the opportunity just for a few seconds to emphasize something I
mentioned early on. And that is we should not assume that if we
have a 6-month lead, if the virus evolves in a rather less-
than-abrupt but more gradual way, which is likely that it
would, and we press the button and say we are going to go full-
scale now, even with that, the capacity for the number of doses
we would have is still an important limiting factor. So it
isn't as if overnight we are going to be able to get a vaccine
for everyone who would need a vaccine. That is very important.
The reason I bring it up--that is the bad news. The news that
should spur us to do what we have spoken certainly to members
of this committee before is by linking our preparedness for the
regular, seasonal influenza with the preparedness for pandemic
flu so that gradually we increase the usage of, the consistency
of demand for, and the capacity for influenza vaccine such that
we have a situation that on a regular year we are making 150
million, 180 million. That would put us in much better stead to
be able to respond in a very quick way if we indeed have to
respond to a pandemic flu. That is extremely important.
Mr. Allen. Okay. Thank you. Dr. Gellin, any difference of
opinion?
Mr. Gellin. No difference of opinion, but I want to sort of
qualify and add a few things to what Drs. Gerberding and Fauci
said. I think it is important to think about the entire
timeframe. You signaled when it starts and when we have
something. I think that really reinforces the importance of
surveillance, to have the eyes, ears, and hands, and labs out
there that can find that virus soon. And I think that we have
gone ahead with this H5 projects, the several H5 projects
really are evidence of that.
The other piece is recognizing that when vaccine starts to
come off the line that it is going to take a while for it to
come off, which is again why a system other than eggs where you
can have multiple things going on in parallel so the time to
the first dose may be the same, but the number of doses you get
subsequently may be greatly increased.
Mr. Allen. Thank you. Let me do a related question. Because
of concerns about how long it might take to develop a pandemic
strain vaccine, the U.K. and France among other countries have
already ordered sufficient supply of Tamiflu for about one-
fourth of their population. And according to press reports, the
U.S. has only ordered for 1 percent of the population. Should
we create a larger stockpile of Tamiflu? What is the timetable
for ordering more supply? And sort of what level of funding
would be necessary to do that?
Ms. Gerberding. We have made the decision to increase our
stockpile. Again, part of the resources that came through the
supplement just recently, the last couple of weeks, may be used
to do that. And we also intend to purchase more stockpile
materials to combat flu and----
Mr. Allen. Is there a number? About how much more do you
think?
Ms. Gerberding. I am not ready to give you an exact number
today.
Mr. Gellin. Let me make a distinction, which is important,
because of what you have cited in the press. The difference
between orders and actual what you have in stock, we have been
worried about this for some period of time and went ahead and
have secured the over two million treatment courses, enough to
treat over two million people. And while other countries have
signaled their intent to purchase more, it is going to be
several years until that is delivered. I am sure the companies
can fill you in on that. And in the meantime few are going to
have to have a strategy to be able to prioritize those who
would be first in line in a limited supply. But I think that is
where our--we have actually emphasized both the antivirals and
the vaccine, recognizing that these are the only two medical
countermeasures that we might have, neither of them perfect,
but we need to do what we could with both of them.
Mr. Allen. Thank you all.
Mr. Ferguson. Ms. Baldwin.
Ms. Baldwin. Thank you, Mr. Chairman. I wanted to further
pursue two of the questions that I raised in my opening
statement. First, regarding planning and preparedness on a
global scale--and I was pleased to hear in your testimony about
Secretary Leavitt addressing the World Health Assembly and
elevating this issue.
Some of the experts at home and abroad have even gone as
far as describing what a formalized global flu pandemic effort
should look like, including some sort of global taskforce,
outbreak management teams with some sort of centralized
management. Is anything happening to achieve these right now,
and does anything like what I have just described exist?
Ms. Gerberding. Thank you. I attended the World Health
Assembly with Dr. Gellin and Secretary Leavitt and others this
year. I also attended the assembly last year, and I can tell
you that there has been a sea change of interest and focus on
influenza in the last year. The meetings were incredibly well-
attended and some very specific actions, steps, and subsequent
plans were laid out that I think will lead to action.
But what we are doing, in addition to what the World Health
Organization is doing, is to use the supplemental resources
that we were provided, $15 million this past week to CDC and
another $10 million to USAID to specifically focus right now on
Southeast Asia. And we are in the process of developing very
specific capabilities that would include improving the local
ability to identify cases and to get the frontline lab test
done, as well as augmenting the training of the many health
aids and clinicians and public health officials that would need
to engage to improve the infrastructure, particularly in the
Mekong Delta countries.
So we haven't finalized that plan; we are still working on
it because we are working in collaboration with USAID and the
Department of Defense as well as the Ministers of Health and
the World Health Organization. But I think this is going to
give us a giant step forward in our ability to do something
right now in the region to really do exactly what you are
suggesting needs to be done.
Mr. Gellin. And if I could, I will just speak to that in a
different way. The World Health Organization in 1999 put out
the first Pandemic Influenza Preparedness Plan framework and
asked that all countries follow that. As you can imagine, that
would ease communication when people would have a similar
understanding of where they were in a pandemic. They regionally
revised that, and I think it was last December or January,
which again forces us to change our plan, which speaks again to
the fact that these plans will continue to evolve. But again
the one that will come out this summer will follow the WHO
framework.
I think it does speak to what Dr. Gerberding mentioned and
reinforced that people recognize the definition of a pandemic
is a global problem, and all the countries, those affected and
those who might be affected, are in this together.
Ms. Gerberding. I got the International Health Regulations
approved at the World Health Assembly so member nations voted
approval of new requirements that would mandate countries to
report any condition that could pose an international health
threat with specific mention of influenza and SARS-like
illness.
Ms. Baldwin. Thank you. The other issue that I wanted to
pursue in greater depth--this question is for you, Dr. Gellin--
is the component of public education preparedness in that
sense. And I think back to how information was disseminated
when we had the anthrax attacks, what level of preparation
there was for that in terms of public awareness. And obviously
there was certainly some elements of panic, et cetera. Tell me
if you will--and you alluded to this in your testimony that
there are elements in place and moving forward--what are they?
What sort of strategies do you have to educate the public and
maybe also working with the media?
Mr. Gellin. Well, I think there is a lot that has begun to
be put in place, and I guess I would actually put it in terms
of a two-way discussion. Education sounds like we are going to
tell you what we know, but we also want to have that as a
discussion that goes both ways. So there are a number of things
that are now being developed. There are going to be some--I
mean I don't know if they are precisely town hall meetings, but
ways to go out and have discussion with representatives of the
public. I think part of the challenge is going to be the
separation of pandemic influenza from regular influenza,
recognizing the challenges of that every year.
And I think it was ironic that last year, when we put out
our draft plan on August 26, it was the day that Chiron first
announced that they were having trouble. So our intention to
put that plan out away from the flu season specifically to try
to separate pandemic influenza from influenza changed. But I
think that we are probably all living with the fact that
influenza and pandemic influenza seem to be everyday
discussions.
Ms. Baldwin. Have these town hall meetings begun to happen
or are they in the pipeline? What----
Mr. Gellin. In the pipeline. The----
Ms. Gerberding. There are other things that have been going
on as well. We have ongoing focus groups, particularly in
follow-up to last year's flu vaccine. One critical question we
need to know is will clinicians still want to offer flu
vaccine. So we have been doing surveys to get answers to what
will target audiences do under various circumstances of supply
or severity of flu.
We have also, through out preparedness investments in the
States, created a whole curriculum on risk communication, and
all States now have risk communicators in the State Health
Department or the Governor's office who are experienced at
explaining things to the public in times of high stress and
emotional conduct. And we have exercised those.
Unfortunately, many times in the last several months
through the many non-flu-related outbreaks and tsunamis and
hurricanes that we have experienced, but we are finding that
capacity has grown dramatically since anthrax. We know from
that kind of formative research that although government
leaders are very important in setting the stage for the
communication, the person that people most want to hear
information from is their own doctor. And so targeting the
clinicians as a component of the educational--it is absolutely
critical at the local level.
Mr. Ferguson. With that we will conclude our first panel. I
want to thank our witnesses, Dr. Gerberding, Dr. Fauci, Dr.
Gellin, thank you very much for being here today. Thank you for
the work that you do on behalf of the healthcare of the
American people. And I will invite the witnesses for our second
panel to come to the witness table. I know Chairman Deal had
introduced our second panel earlier in the hearing but very
briefly by way of introduction, our second panel includes Dr.
Marcia Crosse, the Director of Health Care Issues at GAO; Mr.
Phillip Hosbach, Vice President of Immunization Policy and
Government Relations at sanofi pasteur; Dr. Ralph Tripp,
Professor and GRA Chair at the University of Georgia College of
Veterinary Medicine, Department of Infectious Diseases; Dr.
Andrew Pavia, Infectious Diseases Society of America; and Dr.
Dominick Iacuzio, Medical Director at Hoffmann-La Roche. Thank
you all very much for being here. We appreciate your presence.
Dr. Crosse, we will begin with you. Just turn on your
microphone if you would. Thank you.
STATEMENTS OF MARCIA CROSSE, DIRECTOR, HEALTH CARE ISSUES,
UNITED STATES GOVERNMENT ACCOUNTABILITY OFFICE; ANDREW T.
PAVIA, CHAIRMAN, TASKFORCE ON PANDEMIC INFLUENZA, INFECTIOUS
DISEASES SOCIETY OF AMERICA, AND PROFESSOR AND CHIEF, DIVISION
OF PEDIATRIC INFECTIOUS DISEASES, UNIVERSITY OF UTAH MEDICAL
CENTER; PHILLIP HOSBACH, VICE PRESIDENT, IMMUNIZATION POLICY
AND GOVERNMENT RELATIONS, SANOFI-PASTEUR; DOMINICK A. IACUZIO,
MEDICAL DIRECTOR, HOFFMANN-LA ROCHE; AND RALPH A. TRIPP,
CHAIRMAN, GEORGIA RESEARCH ALLIANCE, AND PROFESSOR, DEPARTMENT
OF INFECTIOUS DISEASES, UNIVERSITY OF GEORGIA, COLLEGE OF
VETERINARY MEDICINE
Ms. Crosse. I am pleased to be here today as you discuss
issues regarding our preparedness to respond to an influenza
pandemic. We have heard today already about the threat posed by
Avian Influenza. As many members noted, while the extent of the
next pandemic cannot be predicted, modeling studies suggest
that its effects in the United States could be severe.
You asked us to provide our perspective on the Nation's
ability to conduct disease surveillance for an influenza
pandemic, as well as preparedness for such a pandemic. In my
testimony I will briefly discuss surveillance systems and the
challenges that remain in preparedness and response.
There are a number of systems in place to identify
influenza outbreaks abroad, to alert us to a pandemic, and
these systems generally appear to be working well. HHS has
taken important steps to enhance surveillance. Given the global
nature of disease, a pandemic that begins abroad could quickly
spread to this country. Public health officials plan to rely on
the Nation's existing influenza surveillance system and recent
enhancements to identify an influenza pandemic. CDC currently
collaborates with multiple public health partners, as we heard,
including WHO to obtain data that provide national and
international pictures of influenza activity.
Public health officials and healthcare organizations have
undertaken several initiatives that may be expected to enhance
influenza surveillance. While some of these initiatives are
focused more generally on increasing preparedness for
bioterrorism and emerging infectious diseases, others have been
undertaken specifically in preparation for an influenza
pandemic. For example, in response to concerns over the past
few years about Avian Influenza, CDC implemented an initiative
in cooperation with WHO to improve influenza surveillance in
Asia, which Dr. Gerberding discussed.
CDC has also implemented initiatives to improve public
health communications systems it uses to collect and
disseminate surveillance information for many diseases. In
addition, CDC, FDA, and the Department of Agriculture have made
efforts to enhance their coordination of surveillance efforts
for animal diseases that can be transferred to humans such as
SARS and certain strains of influenza.
While public health officials have undertaken several
initiatives to enhance influenza surveillance capabilities,
challenges remain with regard to other aspects of preparedness
and response. The steps HHS is taking to address these
challenges may not be in place in time to fill the current gaps
in preparedness should an influenza pandemic occur in the next
several years.
One area of concern is the supply of vaccine and antiviral
drugs. As we learned in the 2004-2005 influenza season, the
vaccine supply is fragile. It takes many months to produce
vaccine and problems with even a single manufacturer can result
in vaccine shortages.
Further, as was extensively discussed in the first panel,
our current stockpile of antiviral drugs is insufficient to
meet the likely demand in a pandemic. HHS is working to expand
vaccine production capacity and to stockpile vaccine and
antiviral drugs, but it will be years before these preparations
are in place.
Other challenges in preparedness and response exist across
the public and private sectors. Regulatory, privacy, and
procedural issues surrounding measures to control the spread of
disease must be addressed. And both the public and private
sectors must resolve issues related to an insufficient hospital
capacity and health workforce for responding to a large-scale
outbreak such as an influenza pandemic. A pandemic would have
major impacts on the ability of communities to respond,
businesses to function, and public safety to be maintained.
Finally, since 2000 we have been urging the department to
complete its pandemic plan. A draft plan was issued in August
2004, but the plan has not been finalized. Our concern is not
whether the plan is modified and updated on the basis of
experience or events, but absent a completed Federal plan, key
questions remain unanswered. Some decisions yet to be made
include: determining the Federal role and the public versus
private sector role in the purchase, distribution, and
administration of vaccines and antiviral drugs; how population
groups will be prioritized for vaccination; what quarantine
authorities or travel restrictions may need to be invoked; and
how Federal resources should be deployed during a pandemic. It
is important for the Federal Government and the States to work
through these issues before we are in a time of crisis.
Mr. Chairman, this concludes my prepared statement. I would
be happy to answer any questions you or other members of the
subcommittee may have. Thank you.
[The prepared statement of Marcia Crosse follows:]
Prepared Statement of Maria Crosse, Director, Health Care, Uited States
Government Accountability Office
Mr. Chairman and Members of the Subcommittee: I am pleased to be
here today as you discuss issues regarding the nation's preparedness to
respond to a worldwide influenza epidemic, or influenza
pandemic.1 The emergence of new diseases such as severe
acute respiratory syndrome (SARS) has raised concerns about our ability
to respond to other infectious disease outbreaks such as an influenza
pandemic,2 which many experts believe to be inevitable.
Vaccine shortages and distribution problems during the 2004-2005
influenza season add to these concerns.
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\1\ An influenza pandemic is defined by the emergence of a novel
influenza virus, to which much or all of the population is susceptible,
that is readily transmitted person-to-person and causes outbreaks in
multiple countries.
\2\ See GAO, SARS Outbreak: Improvements to Public Health Capacity
Are Needed for Responding to Bioterrorism and Emerging Infectious
Diseases, GAO-03-769T (Washington, D.C.: May 7, 2003).
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Influenza pandemics arise periodically but unpredictably from a
major genetic change in the virus that results in a new
strain.3 Some experts believe that the next pandemic could
be spawned by the recurring avian influenza in Asia. As of May 19,
2005, 97 people, mostly young and otherwise healthy, have been
confirmed by the World Health Organization (WHO) to have been infected
with avian influenza since 2003, and 53 of them have died. Recent
studies suggest that avian influenza strains are increasingly capable
of causing severe disease in humans and suggest that these strains have
become endemic in some wild birds. If these avian influenza strains
directly infect humans and acquire the ability to be readily
transmitted between people, a pandemic could occur.
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\3\ Influenza pandemics can have successive ``waves'' of disease
and last for up to 3 years. Three pandemics occurred in the 20th
century: the ``Spanish flu'' of 1918, which killed 500,000 people in
the United States; the ``Asian flu'' of 1957, which caused 70,000
deaths in the United States; and the ``Hong Kong flu'' of 1968, which
caused 34,000 deaths in the United States.
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While the severity of the next pandemic cannot be predicted,
modeling studies suggest that its effect in the United States could be
severe. The Centers for Disease Control and Prevention (CDC) estimates
that if a ``medium-level'' influenza pandemic were to occur in the
United States, in the absence of any control measures (e.g.,
vaccination and drugs), it could cause 89,000 to 207,000 deaths,
314,000 to 734,000 hospitalizations, 18 million to 42 million
outpatient visits, and another 20 million to 47 million cases of the
illness.4 From 15 percent to 35 percent of the U.S.
population could be affected by an influenza pandemic, with associated
costs ranging from $71 billion to $167 billion.
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\4\ See CDC, Fact Sheet, Information about Influenza Pandemics, 3,
www.cdc.gov/flu, downloaded May 12, 2005.
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You asked us to provide our perspective on the nation's ability to
conduct disease surveillance 5 for an influenza pandemic, as
well as the public health system's preparedness for an influenza
pandemic. In this testimony, I will discuss (1) surveillance systems in
place to identify and monitor an influenza pandemic and (2) challenges
in preparedness and response to an influenza pandemic.
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\5\ Disease surveillance is the process of reporting, collecting,
analyzing, and exchanging information related to cases of infectious
diseases.
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My testimony today is based largely on our 2004 report on disease
surveillance 6 as well as reports and testimony on influenza
outbreaks, influenza vaccine supply, pandemic planning, and the SARS
outbreak that we have issued since October 2000 7 and work
we have conducted to update key information. Our prior work on disease
surveillance and influenza pandemics included analysis of information
provided by multiple federal departments and agencies, including the
Department of Health and Human Services (HHS)--specifically from CDC
and the Food and Drug Administration (FDA)--and the Departments of
Agriculture, Defense, and Homeland Security, as well as interviews with
officials of those departments and agencies. We also interviewed public
health department officials from 11 states,8 vaccine
manufacturers, and vaccine distributors and surveyed physician group
practices. To learn about pandemic planning efforts, we interviewed HHS
officials in the National Vaccine Program Office and reviewed HHS's
August 2004 draft ``Pandemic Influenza Preparedness and Response
Plan.'' Our prior work on the SARS outbreak included analysis of
information provided by U.S. agencies, WHO, and Asian governments, as
well as interviews with officials from those entities. We also
conducted fieldwork on SARS in Beijing; Hong Kong; Guangdong Province,
China; and Taipei, Taiwan. In May 2005, we updated our information to
include issues that arose during the 2004-2005 influenza season and to
verify the current status of HHS efforts on surveillance, planning, and
preparedness activities. We conducted all of our work in accordance
with generally accepted government auditing standards.
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\6\ See GAO, Emerging Infectious Diseases: Review of State and
Federal Disease Surveillance Efforts, GAO-04-877 (Washington, D.C.:
Sept. 30, 2004).
\7\ See ``Related GAO Products'' at the end of this testimony for a
list of our earlier work related to emerging infectious diseases and
influenza pandemic planning.
\8\ These states--California, Colorado, Indiana, Louisiana,
Minnesota, New York, Pennsylvania, Tennessee, Texas, Washington, and
Wisconsin--were selected based on their participation in CDC's Emerging
Infections Program, each state's most recent infectious disease
outbreak, and their geographic location.
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In summary, federal public health officials plan to rely on the
nation's existing influenza surveillance system and enhancements to
identify an influenza pandemic. CDC currently collaborates with
multiple public health partners, including WHO, to obtain data that
provide national and international pictures of influenza activity.
Federal public health officials and health care organizations have
undertaken several initiatives that are intended to enhance influenza
surveillance capabilities. While some of these initiatives are focused
more generally on increasing preparedness for bioterrorism and other
emerging infectious disease health threats, others were undertaken in
preparation for an influenza pandemic. For example, in response to
concerns over the past few years about the potential for avian
influenza to become the next influenza pandemic, CDC implemented an
initiative in cooperation with WHO to improve influenza surveillance in
Asia. CDC has also implemented initiatives to improve the
communications systems it uses to collect and disseminate surveillance
information. In addition, CDC, USDA, and FDA have made efforts to
enhance their coordination of surveillance efforts for diseases that
arise in animals and can be transferred to humans, such as SARS and
certain strains of influenza with the potential to become pandemic.
While public health officials have undertaken several initiatives
to enhance influenza surveillance capabilities, challenges remain with
regard to other aspects of preparedness for and response to an
influenza pandemic. In particular, HHS has not finalized planning for
an influenza pandemic. In 2000, we recommended that HHS complete the
national plan for responding to an influenza pandemic, but the plan has
been in draft format since August 2004. Absent a completed federal
plan, key questions about the federal role in the purchase,
distribution, and administration of vaccines and antiviral drugs during
a pandemic remain unanswered. Other challenges with regard to
preparedness for and response to an influenza pandemic exist across the
public and private sectors, including challenges in ensuring an
adequate and timely influenza vaccine and antiviral supply; addressing
regulatory, privacy, and procedural issues surrounding measures to
control the spread of disease, for example, across national borders;
and resolving issues related to an insufficient hospital and health
workforce capacity for responding to a large-scale outbreak such as an
influenza pandemic.
BACKGROUND
To be prepared for major public health threats such as an influenza
pandemic, public health agencies need several basic capabilities,
including disease surveillance systems. Specifically, to detect cases
of pandemic influenza, especially before they develop into widespread
outbreaks, local, state, and federal public health officials as well as
international organizations collect, analyze, and share information
related to cases of the disease. When effective, surveillance can
facilitate timely action to control outbreaks and promote informed
allocation of resources to meet changing disease conditions.
Influenza
Influenza is more severe than some other viral respiratory
infections, such as the common cold. Most people who get influenza
recover completely in 1 to 2 weeks, but some develop serious and
potentially life-threatening medical complications, such as pneumonia.
People aged 65 and older, people of any age with chronic medical
conditions, children younger than 2 years, and pregnant women are more
likely than other people to develop severe complications from
influenza. Influenza and pneumonia rank as the fifth leading cause of
death among persons aged 65 and older.
Influenza viruses undergo minor but continuous genetic changes from
year to year. Almost every year, an influenza virus causes acute
respiratory disease in epidemic proportions somewhere in the world.
Vaccination is the primary method for preventing influenza and its more
severe complications. Influenza vaccine is produced and administered
annually to provide protection against particular influenza strains
expected to be prevalent that year. Influenza vaccine takes several
months to produce. Deciding which viral strains to include in the
annual influenza vaccine depends on data collected from domestic and
international surveillance systems that identify prevalent strains and
characterize their effect on human health. FDA decides which strains to
include in the vaccine and also licenses and regulates the
manufacturers that produce the vaccine.9 HHS has limited
authority, however, to directly control influenza vaccine production
and distribution.10
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\9\ FDA decides which strains to include in the annual influenza
vaccine based on the recommendations of its Vaccines and Related
Biological Products Advisory Committee.
\10\ Under the Federal, Food, Drug and Cosmetic Act, FDA ensures
compliance with good manufacturing practices and has limited authority
to regulate the resale of prescription drugs, including influenza
vaccine, that have been purchased by health care entities, such as
public or private hospitals. The term ``health care entity'' does not
include wholesale distributors. This authority would not extend to
resale of the vaccine for emergency medical reasons. CDC also has a
role in encouraging appropriate public health actions.
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FDA has approved four antiviral medications (amantadine,
rimantadine, oseltamivir, and zanamivir) for prevention and treatment
of influenza. However, influenza virus strains can become resistant to
one or more of these drugs, and so they may not always be effective.
Disease Surveillance and Response
In the United States, responsibility for disease surveillance is
shared--involving health care providers; more than 3,000 local health
departments, including county, city, and tribal health departments; 59
state and territorial health departments; more than 180,000 public and
private laboratories; and public health officials from multiple federal
departments and agencies.
States, through the use of their state and local health
departments, have principal responsibility for protecting the public's
health and therefore take the lead in conducting disease surveillance
and supporting response efforts. According to the Institute of Medicine
(IOM), most states require health care providers to report any unusual
illnesses or deaths--especially those for which a cause cannot be
readily established--to their local and/or state health
department.11 Generally, local health departments are
responsible for conducting initial investigations into reports of
infectious diseases. Laboratory personnel test clinical and
environmental samples for possible exposures and identification of
illnesses. Epidemiologists in health departments use disease
surveillance systems to detect clusters of suspicious symptoms or
diseases in order to facilitate early detection and treatment. Local
and state health departments monitor disease trends. Local health
departments are also responsible for sharing information they obtain
from providers or other sources with their state departments of health.
State health departments are responsible for collecting surveillance
information--which they share on a voluntary basis with CDC and
others--from across their state and for coordinating investigations and
response efforts. Public health officials provide needed information to
the clinical community and the public.
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\11\ The requirement to report clinically anomalous symptoms is
particularly important for the detection of emerging infectious
diseases, many of which may be unfamiliar to health care providers.
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At the federal level, several departments and agencies are involved
in disease surveillance and response. For example,
HHS has primary responsibility for coordinating the nation's response
to public health emergencies. As part of its mission, the
department has a role in planning to prepare for and respond to
an influenza pandemic. One action the department has taken is
the development of a draft national pandemic influenza plan,
titled ``Pandemic Influenza Preparedness and Response Plan.''
CDC is charged with protecting the nation's public health by
directing efforts to prevent and control diseases and
responding to public health emergencies. It has primary
responsibility for conducting national disease surveillance and
developing epidemiological and laboratory tools to enhance
disease surveillance. CDC also provides an array of technical
and financial support for state infectious disease surveillance
efforts. In addition, CDC participates in international disease
and laboratory surveillance sponsored by WHO.
FDA is responsible for ensuring that new vaccines and drugs are safe
and effective and for conducting research on diagnostic tools
and treatment of disease outbreaks. The agency also regulates
and licenses vaccines and antiviral agents through the Center
for Biologics Evaluation and Research and the Center for Drug
Evaluation and Research, respectively. FDA also develops
influenza viral reference strains and reagents and makes them
available to manufacturers for vaccine development and
evaluation.
The Department of Defense (DOD) contributes to global disease
surveillance, training, research, and response to emerging
infectious disease threats. DOD maintains the DOD Influenza
Surveillance Program, a laboratory-based surveillance program.
DOD maintains multiple sites throughout the world that serve as
sentinels for disease outbreaks, where it collects and analyzes
viral specimens.
The Department of Agriculture (USDA) is responsible for protecting
and improving the health and marketability of animals and
animal products by preventing, controlling, and eliminating
animal diseases. USDA undertakes disease surveillance and
response activities to protect U.S. livestock, ensure the
safety of international trade, and contribute to the national
zoonotic disease 12 surveillance effort.
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\12\ Zoonotic diseases are those diseases that are transmitted from
animals to humans.
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The United States is a member of WHO, which is responsible for
coordinating international disease surveillance and response efforts.
An agency of the United Nations, WHO administers the International
Health Regulations, which outline WHO's role and the responsibility of
member countries and regions in preventing the global spread of
infectious diseases. WHO also helps marshal resources from its members
to control outbreaks within individual countries or regions. In
addition, WHO works with national governments to improve their
surveillance capacities through--for example--assessing and redesigning
national surveillance strategies, offering training in epidemiologic
and laboratory techniques, and emphasizing more efficient communication
systems.
EXISTING INFLUENZA SURVEILLANCE SYSTEM AND ENHANCEMENTS WOULD BE USED
TO IDENTIFY AN INFLUENZA PANDEMIC
Surveillance is a key component in planning for an influenza
pandemic, and federal public health officials plan to rely on the
nation's existing annual influenza surveillance system and enhancements
to identify an influenza pandemic. Federal public health officials have
undertaken several initiatives that are intended to enhance influenza
surveillance capabilities. These initiatives have been undertaken both
through programs specific to influenza as well as through programs
focused more generally on increasing preparedness for bioterrorism and
other emerging infectious disease health threats. Federal officials
have implemented and expanded syndromic surveillance systems
13 in order to detect outbreaks more quickly, but there are
concerns that these systems are costly to run and still largely
untested. Federal officials have also implemented initiatives designed
to improve public health communications and have undertaken initiatives
intended to improve the coordination of zoonotic surveillance efforts.
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\13\ Many syndromic surveillance systems currently in use in the
United States were developed in response to the September 11, 2001,
attacks on the World Trade Center and Pentagon and to the anthrax
outbreaks that occurred shortly afterwards. The fundamental objective
of syndromic surveillance is to identify illness clusters early, before
diagnoses are confirmed and reported to public health agencies.
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Systems Are in Place to Routinely Monitor for Influenza
Current U.S. surveillance for identifying annual influenza
outbreaks as well as an influenza pandemic involves multiple public
health partners at all levels of government and relies on several data
sources. At the federal level, CDC's Influenza Branch leads the
national influenza surveillance effort, monitoring disease and viral
trends using data submitted each week from October through May. These
surveillance data are collected at the local and state levels and
voluntarily submitted to CDC. Data submitted on influenza activity in
the United States include data from more than 120 laboratories and
2,000 health care providers and mortality reports from 122 cities. In
addition, influenza data are collected from all 50 state health
departments and the health departments in the District of Columbia and
New York City. CDC also receives data that are specifically focused on
influenza in pediatric patients. When the data are used collectively,
they provide a national picture of influenza activity. Specifically,
they allow CDC to (1) identify when and where influenza activity is
occurring, (2) determine what strains of the influenza virus are in
circulation, (3) detect changes in the influenza virus, (4) monitor
flu-related illnesses, and (5) measure the impact influenza is having
on deaths in the United States.
DOD also plays a role in national and international influenza
surveillance. Specifically, DOD's Influenza Surveillance Program, under
the direction of the Air Force, collects viral specimens from its
active duty personnel and their dependents at military facilities
around the world. DOD's program also sends specimens to CDC for further
analysis and contributes to the determination of which viral strains
FDA includes in the nation's annual influenza vaccine. Internationally,
DOD provides viral specimens to WHO and assists in identifying emerging
influenza strains.
In countries throughout the world, infectious disease surveillance
is a national responsibility, but WHO assists its members' efforts
through its Global Influenza Surveillance Network. WHO's Network is
composed of 112 institutions, called National Influenza Centres, from
83 countries. Collectively, these Centres monitor influenza activity
and annually gather more than 175,000 viral specimens for analysis from
patients with influenza-like illnesses throughout the world. Selected
influenza isolates--an estimated 2,000 viruses--may also be sent to one
of four WHO Collaborating Centres 14 for further, more
specific genetic analysis. The additional analysis conducted by the WHO
Collaborating Centers is used for the annual WHO recommendations on
which strains to include in the influenza vaccine for the northern and
southern hemispheres. In addition to making recommendations on the
components of the influenza vaccine, this Global Influenza Surveillance
Network also serves as a global alert mechanism for the emergence of
influenza viruses with pandemic potential.
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\14\ A WHO Collaborating Centre is a national institution
designated by WHO to form part of an international collaborative
network that contributes to implementing WHO's program priorities and
to strengthening institutional capacity in countries and regions.
Collaborating Centre activities include collection and dissemination of
information, education and training, and participation in collaborative
research developed under WHO's leadership. The four Collaborating
Centres that are part of WHO's Global Influenza Surveillance Network
are located in the United States, Australia, Japan, and the United
Kingdom.
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Federal Agencies Have Undertaken Initiatives to Enhance Influenza
Surveillance
CDC has undertaken several initiatives that are intended to enhance
influenza surveillance capabilities in preparation for an influenza
pandemic. CDC works with its international partners to improve global
surveillance for influenza. For example, CDC participates in
international disease and laboratory surveillance sponsored by WHO.
Also, when concerns were raised over recent influenza seasons that the
avian influenza A (H5N1) could become the next influenza pandemic, CDC
led a variety of efforts with its international partners to plan for
and address threats of increased influenza activity worldwide. For
example, CDC worked collaboratively with WHO to conduct investigations
of avian influenza A in Vietnam and to provide laboratory testing. CDC
also provided training assistance and has implemented an initiative to
improve influenza surveillance in Asia.
CDC also supports several domestic initiatives to improve
surveillance capabilities for influenza. For example, CDC supports
enhanced influenza surveillance activities through its Epidemiology and
Laboratory Capacity (ELC) Grants. Established in 1997, this program
provides funding to state and local influenza programs. Grants have
steadily increased from the first awards in 1997, when less than
$100,000 was provided to five states through August 2004, with funding
totaling more than $2 million being given to about 47 states or major
metropolitan areas. States and cities receiving ELC-influenza funding
are encouraged to achieve three highlighted influenza epidemiology and
laboratory surveillance capacities: sentinel physician surveillance,
viral isolation and subtyping, and year-round surveillance. Each state
targets funding to meet one or more of these three priorities and uses
funding for support of improvements that include the assignment or
hiring of an influenza coordinator, recruitment of sentinel physicians
to collect influenza specimens and report influenza-like illness to the
state, laboratory infrastructure enhancements to increase influenza
testing capabilities for viral isolation and subtyping, and expansion
of influenza surveillance activities to year-round.
In an effort to enhance the ability to detect infectious disease
outbreaks, particularly in their early stages, federal funding has
supported state efforts to implement numerous syndromic surveillance
systems. These systems collect information on syndromes from a variety
of sources. For example, the National Retail Data Monitor (NRDM)
collects data from retail sources instead of hospitals. As of February
2004,--NRDM collected sales data from about 19,000 stores, including
pharmacies, in order to monitor sales patterns in such items as over-
the-counter influenza medications for signs of a developing infectious
disease outbreak.
CDC is taking steps to enhance its two public health communications
systems, the Health Alert Network (HAN) 15 and the Epidemic
Information Exchange (Epi-X),16 which are used in disease
surveillance and response efforts. For example, CDC is working to
increase the number of HAN participants who receive assistance with
their communication capacities. In addition, following reports of human
deaths from avian influenza A in Vietnam in August 2004, CDC issued a
HAN message reiterating criteria for domestic surveillance, diagnostic
evaluation, and infection control precautions. CDC also issued detailed
laboratory testing procedures for avian influenza through HAN.
Similarly, CDC has expanded Epi-X by giving officials at other federal
agencies and departments, such as DOD, the ability to use the system.
CDC is also adding users to Epi-X from local health departments, giving
access to CDC staff in other countries, and making the system available
to Field Epidemiology Training Programs (FETP) located in 21
countries.17 Finally, CDC is facilitating Epi-X's interface
with other data sources by allowing users to access the Global Public
Health Intelligence Network (GPHIN), the system that searches Web-based
media for information on infectious disease outbreaks worldwide.
---------------------------------------------------------------------------
\15\ The Health Alert Network (HAN) is an early-warning and
response system operated by CDC that is designed to ensure that state
and local health departments as well as other federal agencies and
departments have timely access to emerging health information.
\16\ The Epidemic Information Exchange (Epi-X) is a secure, Web-
based communication system operating in all 50 states. CDC uses this
system primarily to share information relevant to disease outbreaks
with state and local public health officials and with other federal
officials. Epi-X also serves as a forum for routine professional
discussions and nonemergency inquiries.
\17\ In selected foreign locations, CDC operates international
training programs, such as FETP. Through FETP, each year CDC trains
approximately 50 to 60 physicians and social scientists in applied
public health, integrating disease surveillance, applied research,
prevention, and control activities. Graduates of the FETP program serve
in their native country and provide links between CDC and their
respective ministries of health. CDC officials said that trainees from
its international programs have frequently provided important
information on disease outbreaks.
---------------------------------------------------------------------------
In addition to the efforts to enhance communication systems,
federal public health officials also have enhanced federal coordination
for zoonotic disease surveillance and expanded training programs.
According to CDC, nearly 70 percent of emerging infectious disease
episodes during the past 10 years have been zoonotic diseases.
Moreover, recent outbreaks of human disease caused by avian influenza
strains in Asia and Europe highlight the potential for new strains to
be introduced into the population. Surveillance for zoonotic diseases
requires collaboration between animal and human disease specialists.
CDC, USDA, and FDA have made efforts to enhance their coordination of
zoonotic disease surveillance. For example, CDC and UDSA are working
with two national laboratory associations to add veterinary diagnostic
laboratories to the Laboratory Response Network (LRN).18 As
of May 2004, 10 veterinary laboratories had been added to LRN, and CDC
officials told us that they had plans to add more veterinary
laboratories in the future. In addition, CDC officials told us the
agency has appointed a staff person whose responsibility, in part, is
to assist in finding ways to enhance zoonotic disease coordination
efforts among federal agencies and departments and with other
organizations. This person is helping CDC develop a working group of
officials from CDC, USDA, and FDA to coordinate zoonotic disease
surveillance.19 According to CDC officials, the goal of this
working group is to explore ways to link existing surveillance systems
to better coordinate and integrate surveillance for wildlife, domestic
animal, and human diseases. CDC officials also said that the agency is
exploring the feasibility of a pilot project to demonstrate this
proposed integrated zoonotic disease surveillance system. In addition,
USDA officials told us that they hired 23 wildlife biologists in fall
2003 to coordinate disease surveillance, monitoring, and management
activities among USDA, CDC, states, and other federal agencies. While
each of these initiatives is intended to enhance the surveillance of
zoonotic diseases, each is still in the planning stage or the very
early stages of implementation.
---------------------------------------------------------------------------
\18\ To strengthen the nation's capacity to rapidly detect
biological and chemical agents that could be used as a terrorist
weapon, CDC, in partnership with the Federal Bureau of Investigation
and the Association of Public Health Laboratories, created LRN in 1999.
According to CDC, LRN leverages the resources of 126 laboratories to
maintain an integrated national and international network of
laboratories that are fully equipped to respond quickly to acts of
chemical or biological terrorism, emerging infectious diseases, and
other public health threats and emergencies. The network includes
federal, state and local public health, military, and international
laboratories, as well as laboratories that specialize in food,
environmental, and veterinary testing. LRN laboratories have been used
in several public health emergencies. For example, in 2001, a Florida
LRN laboratory discovered the presence of Bacillus anthracis, the
pathogen that causes anthrax, in a clinical specimen it tested.
\19\ This working group was created in response to a congressional
mandate that the Secretary of Health and Human Services, through FDA
and CDC, and USDA, coordinate the surveillance of zoonotic diseases.
Public Health Security and Bioterrorism Preparedness and Response Act
of 2002, Pub. L. No. 107-188, 313, 116 Stat. 594, 674 (2002).
---------------------------------------------------------------------------
USDA also conducts influenza surveillance in domestic animals.
Coordination with USDA is important because a pandemic strain is likely
to arise from genetic mixing of animal and human influenza viruses.
Recent outbreaks in domestic poultry in Asia and Europe associated with
cases of human disease highlight the importance of coordinating
surveillance activities. Surveillance for influenza viruses in poultry
in the United States has increased substantially since the outbreak of
highly pathogenic avian influenza (HPAI) in Pennsylvania and
surrounding states in 1983 and 1984. However, individual states are
generally responsible for the development and implementation of
surveillance programs that are consistent with the size and complexity
of the resident poultry industry.
DESPITE EFFORTS BY FEDERAL OFFICIALS, CHALLENGES REMAIN REGARDING
PREPAREDNESS FOR AND RESPONSE TO AN INFLUENZA PANDEMIC
Challenges regarding the nation's preparedness for and response to
an influenza pandemic remain. Specifically, our prior work has found
that although CDC participated in an interagency working group that
developed the U.S. plan for pandemic preparedness that was posted for
public comment in August 2004, as of May 23, 2005, the plan had not
been finalized. Further, we found that the draft plan does not address
certain critical issues, including how vaccine for an influenza
pandemic will be purchased, distributed, and administered; how
population groups will be prioritized for vaccination; what quarantine
authorities or travel restrictions may need to be invoked; and how
federal resources should be deployed. At the state level, we found that
most hospitals across the country lack the capacity to respond to
large-scale infectious disease outbreaks.
HHS's Pandemic Influenza Plan Remains in Draft and Leaves Many
Important Issues Unresolved
In August 2004, HHS released its national pandemic influenza plan
for comment. The draft ``Pandemic Influenza Preparedness and Response
Plan'' describes HHS's role in coordinating a national response to an
influenza pandemic and provides guidance and tools to promote pandemic
preparedness planning and coordination at the federal, state, and local
levels, including both the public and the private sectors. However, as
of May 23, 2005, this document remained in draft form. Further,
although the plan is comprehensive in scope, it leaves many important
decisions unresolved about the purchase, distribution, and
administration of vaccines. For example, some decisions yet to be made
include determining the public- versus private-sector roles in the
purchase and distribution of pandemic influenza vaccines; the division
of responsibility between the federal government and the states for
vaccine distribution; and how population groups will be prioritized and
targeted to receive limited supplies of vaccines. Until these key
decisions are made, public health officials at all levels may find it
difficult to plan for an influenza pandemic, and the timeliness and
adequacy of response efforts may be compromised.
The draft plan does not establish a definitive federal role in the
purchase and distribution of vaccines during an influenza pandemic.
Instead, HHS provides options for vaccine purchase and distribution
that include public-sector purchase and distribution of all pandemic
influenza vaccine; a mixed public-private system where public-sector
supply may be targeted to specific priority groups; and maintenance of
the current largely private system. In its draft plan, HHS does not
recommend a specific alternative.
Furthermore, the draft plan delegates to the states responsibility
for distribution of vaccine. The lack of a clearly defined federal role
in distribution complicates pandemic planning for the states.
Furthermore, among the current state pandemic influenza plans, there is
no consistency in terms of their procurement and distribution of
vaccine and the relative role of the federal government. Approximately
half of the states handle procurement and distribution of the annual
influenza vaccine through the state health agency. The remainder either
operate through a third-party contractor for distribution to providers
or use a combination of these two approaches.
Challenges Persist in Ensuring an Adequate and Timely Influenza Vaccine
Supply
Challenges persist in ensuring an adequate and timely influenza
vaccine supply. The number of producers remains limited, and the
potential for manufacturing problems such as those experienced during
the 2004-2005 influenza season is still present. When one
manufacturer's production is affected, providers who order vaccine from
that manufacturer can experience shortages, while providers who receive
supplies from another manufacturer may have all the vaccine they need.
The allocation plan CDC developed for this past season's shortage was
dependent upon voluntary compliance by the private sector and
individuals to forgo vaccination. Most annual influenza vaccine
distribution and administration are accomplished within the private
sector, with relatively small amounts of vaccine purchased and
distributed by CDC or by state and local health departments. In the
United States, 85 percent of vaccine doses are purchased by the private
sector, such as private physicians and pharmacies. HHS has not yet
determined how influenza vaccine will be distributed and administered
during an influenza pandemic.
There are many issues surrounding the production of influenza
vaccine, which will only become exacerbated during an influenza
pandemic. Vaccines, which are considered the first line of defense to
prevent or reduce influenza-related illness and death, may be
unavailable or in short supply. Producing the vaccine is a complex
process that involves growing viruses in millions of fertilized chicken
eggs. Experience has shown that the vaccine production cycle takes at
least 6 to 8 months after a virus strain has been identified, and
vaccines for some influenza strains have been difficult to mass-
produce, causing further delay. The lengthy process for developing a
vaccine may mean that a vaccine would not be available during the
initial stages of a pandemic.
Vaccine shortages during the 2004-2005 influenza season have
highlighted the fragility of the influenza vaccine market and the need
for its expansion and stabilization. Currently only two manufacturers
are licensed to sell their vaccine in the United States.20
Maintaining an influenza vaccine supply is critically important for
protecting the public's health and improving our preparedness for an
influenza pandemic. As a result, according to CDC officials, the agency
plans to alleviate the impact of next year's influenza season by taking
aggressive steps to ensure an expanded influenza supply to protect the
nation. To this end, the agency's fiscal year 2006 budget request
includes an increase of $30 million for CDC to enter into guaranteed
purchase contracts with vaccine manufacturers to ensure the production
of bulk monovalent influenza vaccine. If supplies fall short, this bulk
product can be turned into a finished trivalent influenza vaccine
product for annual distribution. If supplies are sufficient, the bulk
vaccine can be held until the following year's influenza season and
developed into vaccines if the circulating strains remain the same. In
addition, according to CDC, this guarantee will help to expand the
influenza market by providing an incentive to manufacturers to expand
capacity and possibly encourage additional manufacturers to enter the
market. In addition, the fiscal year 2006 budget request includes an
increase of $20 million to support influenza vaccine purchase
activities.
---------------------------------------------------------------------------
\20\ During the 2004-2005 influenza season, the license for a third
manufacturer was suspended by British regulatory authorities due to
safety concerns with the vaccine.
---------------------------------------------------------------------------
Even if sufficient quantities of the vaccine are produced in time,
vaccines against various strains differ in their ability to produce the
immune response necessary to provide effective protection against the
disease. Studies show that it is uncertain how effective a vaccine will
be in preventing or controlling the spread of a pandemic influenza
virus.
Challenges Persist in Ensuring an Adequate Supply of Antiviral Drugs
Early in an influenza pandemic, especially before a vaccine is
available or during a period of limited vaccine supply, use of
antiviral drugs may have a significant effect. Specifically, antiviral
drugs can help prevent or mitigate the number of influenza-related
deaths until an influenza vaccine becomes available. They can be used
against all strains of pandemic influenza and have immediate
availability as both a prophylactic to prevent illness and as a
treatment if administered within 48 hours of the onset of symptoms.
According to HHS, analysis is ongoing to define optimal antiviral use
strategies, potential health impacts, and cost-effectiveness of
antiviral drugs in the setting of a pandemic.
The United States has a limited supply of influenza antiviral
medications stored for an influenza pandemic. HHS officials expect the
amount produced will be below demand during a pandemic. This
assumption, supported by drug manufacturers, is based on the fact that
current production levels of antiviral drugs are set in response to
current demand, whereas demand in a pandemic is expected to increase
significantly if vaccines are unavailable. In addition, the production
of antiviral medications cannot be rapidly expanded and involves a long
production process--at least 6 to 9 months. Moreover, sometimes
influenza virus strains can become resistant to one or more of the four
approved influenza antiviral drugs, and thus the drugs may not always
work. For example, the influenza A (H5N1) viruses identified in human
patients in Asia in 2004 and 2005 have been resistant to two of the
four antiviral drugs, amantadine and rimantadine.
Implementation of Control Measures to Prevent Spread of Pandemic
Influenza Present Difficulties
Another challenge in responding to an influenza pandemic involves
implementing certain control measures to prevent the spread of the
disease. These control measures--case identification and contact
tracing, transmission control, and exposure management--are well-
established and have proved effective in both health care and community
settings.21 Federal attempts to limit the spread of SARS
into the United States by advising passengers who traveled to infected
countries faced multiple obstacles. For example, due to airline
concerns over authority and privacy, as well as procedural constraints,
CDC was unable to obtain passenger contact information it needed to
trace travelers. Although HHS has statutory authority to prevent the
introduction, transmission, or spread of communicable diseases from
foreign countries into the United States,22 HHS regulations
implementing the statute do not specifically provide for HHS to obtain
passenger manifests or other passenger contact information from
airlines and shipping companies for disease outbreak control
purposes.23
---------------------------------------------------------------------------
\21\ In the United States, the Healthcare Infection Control
Practices Advisory Committee, a federal advisory committee made up of
14 infection control experts, develops recommendations and guidelines
regarding general infectious disease control measures for CDC. Expert
recommendations include (1) case identification and contact tracing,
which involves defining what symptoms, laboratory results, and medical
histories constitute a positive case in a patient and tracing and
tracking individuals who may have been exposed to these patients; (2)
transmission control, which involves controlling the transmission of
disease-producing microorganisms through use of proper hand hygiene and
personal protective equipment, such as masks, gowns, and gloves; and
(3) exposure management, which involves separating infected and
noninfected individuals.
\22\ Section 361 of the Public Health Service Act, 42 U.S.C.
264.
\23\ See 42 C.F.R pts 70 and 71; 21 C.F.R. pts 1240 and 1250.
---------------------------------------------------------------------------
Most Hospitals Lack the Capacity to Respond to Large-Scale Infectious
Disease Outbreaks
A challenge identified during the SARS outbreak that may also
affect response efforts during an influenza pandemic is lack of
sufficient hospital and workforce capacity. This lack could be
exacerbated during an influenza pandemic, compared to other natural
disasters, such as a tornado or hurricane, or an intentional release of
a bioterrorist agent, because it is likely that a pandemic would result
in both widespread and sustained effects.
Public health officials we spoke with said a large-scale outbreak,
such as an influenza pandemic, could strain the available capacity of
hospitals by requiring the use of entire hospital sections (along with
their staff) to be used as isolation facilities. As we have reported
earlier, most states lack ``surge capacity,'' that is, the capacity to
respond to the large influx of patients that could occur during a large
public health emergency.24 For example, few states reported
that they had the capacity to evaluate, diagnose, and treat 500 or more
patients involved in a single incident. In addition, few states
reported having the capacity to rapidly establish clinics to immunize
or provide treatment to large numbers of patients. Moreover, a shortage
in workforce could increase during an influenza pandemic because higher
disease rates could result in high rates of absenteeism among health
care workers who are likely to be at increased risk of exposure and
illness.
---------------------------------------------------------------------------
\24\ See GAO, Public Health Preparedness: Response Capacity
Improving, but Much Remains to be Accomplished, GAO-04-458T
(Washington, D.C.: Feb. 12, 2004).
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CONCLUDING OBSERVATIONS
There are a number of systems in place to identify influenza
outbreaks abroad, to alert us to a pandemic, and these systems
generally appear to be working well. HHS has taken important steps to
enhance surveillance and to fund initiatives for preparedness and
response, including steps to increase the vaccine supply.
However, important challenges remain in our preparedness to
respond, should an influenza pandemic occur in the United States. The
steps HHS is taking to address vaccine production capacity and
stockpiling of antiviral drugs may not be in place in time to fill the
current gaps in preparedness should an influenza pandemic occur in the
next several years. As we learned in the 2004-2005 influenza season,
problems affecting even a single manufacturer can produce major
shortages. Once a pandemic influenza strain is identified, a vaccine
will take many months to produce, and our current stockpile of
antiviral drugs is insufficient to meet the likely demand. Pandemic
influenza would have major impacts on the ability of communities to
respond, businesses to function, and public safety to be maintained
when communities across the country are simultaneously impacted and
hospital capacity is overwhelmed.
Since 2000, we have been urging the department to complete its
pandemic plan. A draft plan was issued in August 2004, with a 60-day
period for public comment, but as of this week, the plan had not been
finalized. It is important for the federal government and the states to
work through issues such as how vaccine will be purchased, distributed,
and administered, how population groups will be prioritized for
vaccination, what quarantine authorities or travel restrictions may
need to be invoked, and how federal resources should be deployed before
we are in a time of crisis.
Mr. Chairman, this concludes my prepared statement. I would be
happy to respond to any questions you or other Members of the
Subcommittee may have at this time.
Contact and Staff Acknowledgments
For further information about this testimony, please contact Marcia
Crosse at (202) 512-7119. Gloria E. Taylor, Gay Hee Lee, Elizabeth T.
Morrison, and Roseanne Price made key contributions to this statement.
RELATED GAO PRODUCTS
Emerging Infectious Diseases: Review of State and Federal Disease
Surveillance Efforts. GAO-04-877. Washington, D.C.: September 30, 2004.
Infectious Disease Preparedness: Federal Challenges in Responding
to Influenza Outbreaks. GAO-04-1100T. Washington, D.C.: September 28,
2004.
Emerging Infectious Diseases: Asian SARS Outbreak Challenged
International and National Responses. GAO-04-564. Washington, D.C.:
April 28, 2004.
Public Health Preparedness: Response Capacity Improving, but Much
Remains to Be Accomplished. GAO-04-458T. Washington, D.C.: February 12,
2004.
Infectious Diseases: Gaps Remain in Surveillance Capabilities of
State and Local Agencies. GAO-03-1176T. Washington, D.C.: September 24,
2003.
Severe Acute Respiratory Syndrome: Established Infectious Disease
Control Measures Helped Contain Spread, But a Large-Scale Resurgence
May Pose Challenges. GAO-03-1058T. Washington, D.C.: July 30, 2003.
SARS Outbreak: Improvements to Public Health Capacity Are Needed
for Responding to Bioterrorism and Emerging Infectious Diseases. GAO-
03-769T. Washington, D.C.: May 7, 2003.
Infectious Disease Outbreaks: Bioterrorism Preparedness Efforts
Have Improved Public Health Response Capacity, but Gaps Remain. GAO-03-
654T. Washington, D.C.: April 9, 2003.
Global Health: Challenges in Improving Infectious Disease
Surveillance Systems. GAO-01-722. Washington, D.C.: August 31, 2001.
Flu Vaccine: Steps Are Needed to Better Prepare for Possible Future
Shortages. GAO-01-786T. Washington, D.C.: May 30, 2001.
Flu Vaccine: Supply Problems Heighten Need to Ensure Access for
High-Risk People. GAO-01-624. Washington, D.C.: May 15, 2001.
Influenza Pandemic: Plan Needed for Federal and State Response.
GAO-01-4. Washington, D.C.: October 27, 2000.
West Nile Virus Outbreak: Lessons for Public Health Preparedness.
GAO/HEHS-00-180. Washington, D.C.: September 11, 2000.
Global Health: Framework for Infectious Disease Surveillance. GAO/
NSIAD-00-205R. Washington, D.C.: July 20, 2000.
Mr. Ferguson. Thank you very much. Dr. Pavia.
STATEMENT OF ANDREW T. PAVIA
Mr. Pavia. Yes. Mr. Chairman, members of the committee,
thank you very much for inviting the IDSA to make its opinion
felt and heard about pandemic influenza. I am Andrew Pavia. I
am Chair of the Infectious Diseases Society of America's
Taskforce on Pandemic Influenza and also professor of Pediatric
Infectious Disease and chief at the University of Utah.
IDSA, so that you know, represents over 8,000 infectious
disease experts, including all three of the members of the
first panel and soon to be Mr. Green's daughter, who work in
taking care of patients with the most severe infectious disease
and conducting laboratory research and in public health. And
let me be very clear that although this is a mixed panel, I am
speaking on behalf of the physicians, our patients, and the
public health.
Like everyone else who has spoken today, IDSA believes that
the next pandemic is inevitable, but more importantly, we
believe that the evidence suggests that it may be imminent. We
don't know whether H5N1, Avian Flu, will be the next pandemic
strain. We don't know how severe the next pandemic will be. We
do know, however, that it will occur, and we know that the
severity is going to be somewhere between severe and
catastrophic.
For all that you have heard it is hard to overemphasize or
exaggerate the potential impact of a pandemic. You heard the
figures for CDC's estimate of the mortality and impact of a
moderate pandemic. Their same estimates suggest that if we have
a pandemic with a virus that has the severity equivalent to
1918, that it would result in between .9 and 2.2 million deaths
and four to ten million hospitalizations. Now, imagine the
economic impact of paying for four to ten million
hospitalizations. And I am going to come back to the economics
a little bit because some of the countermeasures require
sufficient funding.
As we think about the economic impact, these figures have
not been fully worked out, but as was pointed out in
yesterday's ``Wall Street Journal'' editorial and by several
analysts, it is likely that even a mild pandemic would bring
global economies to a halt, it would devastate the agriculture,
and it would probably pose a grave threat to national security.
If you think about the costs that we have seen from relatively
mild epidemics before, consider SARS. Fewer than 8,000 people
were sickened and about 800 died, and yet the estimate is that
for countries affected in Southeast Asia, the cost ranged
between .2 and 1.8 percent of their GDP. The city of Toronto
lost over $1 billion alone. These are the kind of figures that
you need to think about when you think about the cost of the
countermeasures.
Now, I want to be very clear that pandemic influenza has
received a great deal of attention from the government, from
Congress, and we are very grateful. And you have heard a great
deal about what is being done at the Federal Government level
in the earlier panel. And I want to point out that NVPO in
particular has taken a leadership position in this, and that is
very, very important. However, as of today, the IDSA believes
that the United States is woefully unprepared for a pandemic
that might occur in the next few years.
We have many recommendations in our written testimony, and
I am going to focus my remaining comments on areas where
scientists alone can't deal with the problem, and it requires
activity by policymakers. The first and foremost is adequate
funding of our public health efforts. And IDSA has recommended
not only restoring the cuts in the CDC budget, but appropriate
increases. And I think that that goes across the board for our
public health infrastructure.
Many have pointed out the fragility of our vaccine supply
as highlighted by the events of last fall. But I think what we
haven't emphasized is that the capacity to produce vaccine is
really the critical issue. And the same holds true for
antivirals. It is assumed by most experts in the event of a
crisis we are going to be totally dependent on what can be
produced domestically. And if we look at the capacity to
produce vaccine domestically, we can make between 60 and 70
million doses of trivalent vaccine. That means that perhaps
with a monovalent vaccine we could produce 180 million doses
after a lag time of about 6 months and a year to produce that
180 million doses. The estimate is we would need two doses for
every man, woman, and child in the United States, or 600
million doses. Clearly, we are either going to have to
dramatically increase the capacity to produce vaccine or the
efficiency with which it can be produced or the number of
people we can immunize with a given amount of vaccine.
To that end a great deal of progress has been made. You
have heard from HHS and from NIH about the beginnings of
programs to fund improvements in the efficacy of vaccine
production and ways to look at antigen-sparing techniques that
would use less vaccine. I think that if we look at it
objectively, when my question, whether it is too little and
whether it might be too late, but in order to have a robust
response we need more capacity to produce vaccine domestically.
That means we need a dramatically greater use of vaccine year-
in, year-out. And to that end I think that Congress can have a
role in increasing incentives for companies to enter the
vaccine market so that we have a more diverse production and
that we use more vaccine in every year.
Now, I think it is also worth pointing out that every
dollar we spend on countermeasures for pandemic flu--I promise
this isn't Avian Influenza--no coughing--that every dollar we
spend on pandemic flu will yield an annual benefit in
preventing lives lost for our yearly flu epidemics.
I want to turn our attention for a moment to stockpile.
That has come up before. And I have to respectfully disagree
with what Dr. Gerberding said earlier. An expert panel that is
advising the National Vaccine Advisory Committee that will go
into the pandemic plan feels that in the first 6 months of an
epidemic the use of antivirals will be a major tool that we
have, if not the only tool, to decrease morbidity and mortality
and to allow the vital functions of government and of the
healthcare system to continue.
To that end we need to have an adequate stockpile. IDSA's
leadership, perhaps as a strawman, has suggested that we
purchase enough antivirals to treat 50 percent of the United
States population. Now, we know that our allies in Europe have
planned on purchasing enough to treat between 20 and 25
percent. All of these numbers are crudely derived. There are
more scientific efforts underway to figure out what the actual
need would be. But it will likely range between 60 million and
150 million doses. The 2.3 million doses we have in the U.S.
stockpile currently are clearly inadequate.
The cost of purchasing antivirals for the stockpile is
going to be considerable. It can't be redirected from existing
health resources. It can't be redirected from within HHS. And
it is going to require considerable outside appropriation. But
as I hope I have made clear, the costs of not doing something
will far exceed the cost of developing a stockpile.
Another issue that is important is that the entire
production of oseltamivir or Tamiflu, as of today, is made in
Switzerland. And as I mentioned earlier, it may not be
available to the United States in a time of crisis.
A question was asked about indemnification earlier. We have
learned from past experiences that in 1976 that the
manufacturers were reluctant to release vaccine in the absence
of liability productions. We learned 2 years ago in the
attempts to provide small pox immunization that hospitals and
providers were reluctant to give small pox vaccine without
having some form of indemnification against problems that
arose.
And a third problem is how are we going to compensate
people who might be injured by an experimental vaccine?
Clearly, we need to have some sort of vaccine injury
compensation coverage for a pandemic vaccine.
Mr. Ferguson. Dr. Pavia, I am just going to ask you to
summarize, please.
Mr. Pavia. Very good. I am going to stop my comments there.
You can tell that I am a professor and used to having the
floor. Only slightly worse, I suppose, than being a member. But
thank you very much for having us and for the attention and the
expertise that you bring today.
[The prepared statement of Andrew T. Pavia follows:]
Prepared Statement of Andrew T. Pavia, Infectious Diseases Society of
America
Chairman Deal, Ranking Member Brown, and Members of the House
Energy and Commerce Health Subcommittee, thank you for inviting the
Infectious Diseases Society of America (IDSA) to present our views on
the U.S. preparedness for pandemic influenza and to allow us to share
with you our perspective on activities needed to strengthen the
nation's current approach. I am Dr. Andrew T. Pavia, chair of IDSA's
Task Force on Pandemic Influenza, and professor and chief of the
Division of Pediatric Infectious Diseases at the University of Utah
Health Sciences Center and Primary Children's Hospital.
IDSA represents nearly 8,000 infectious disease (ID) experts, many
of whom administer the flu vaccine to patients, treat life-threatening
complications of influenza, conduct vaccine and antiviral research, and
implement influenza surveillance activities and other important
influenza public health programs at the local, state, and federal
levels. Let me be very clear from the onset: Although we are speaking
on the same panel as our industry colleagues, our testimony is provided
strictly for the good of public health and the patients whom we treat.
IDSA is not here on behalf of the pharmaceutical or biotechnology
industries nor is our advocacy financed in any way by industry.
idsa is seriously concerned about the next influenza pandemic
Like our colleagues in federal government, we believe that the next
influenza pandemic is imminent. These predictions are primarily based
upon the historic intervals between outbreaks as well as the increased
spread and ominous behavior of the H5N1 avian influenza virus, which
now is endemic among birds in much of Asia. We are very concerned that
the H5N1 avian virus has shown the ability to mutate and has become
capable of infecting mammals, including pigs, tigers, cats, and humans
as well as birds. At least 97 confirmed human cases of H5N1 infections
have been documented by the World Health Organization (WHO) since
January 2004 with 53 deaths. A recent WHO consultants meeting found
evidence of further mutation and a suggestion that person-to-person
transmission might be occurring in Northern Vietnam. Should the virus
become readily transmissible from human to human, the disease could
easily spread beyond Asia's borders and initiate a global pandemic. The
U.S. population has no immunity and therefore no protection against
this deadly virus. Implications of Pandemic Influenza for the United
States
The impact of a pandemic influenza outbreak cannot be
overemphasized. During the past century, influenza pandemics occurred
in 1918, 1957, and 1968, with significant morbidity and mortality in
both high-risk and healthy children and adults. These outbreaks cost
the lives of hundreds of thousands of Americans. Historians now
estimate that between 50 million and 100 million people died as a
result of the 1918 influenza pandemic alone. More than half a million
Americans died, many of them young adults in the prime of life.
Although the 1956 and 1968 pandemics were not as severe, the current
mortality rate among patients with H5N1 influenza is more than 50
percent compared with 2.5 to 5 percent for the disastrous 1918 pandemic
virus. The Centers for Disease Control and Prevention (CDC) has
estimated that a pandemic as severe as the 1918 pandemic would cause
between 0.9 and 2.2 million deaths and 4 million to 10 million
hospitalizations in the United States.
The next pandemic will cause much economic and social chaos. There
will be a dramatic impact on the U.S. and global economies, and
potentially on civil order and international security. Consider the
billions of dollars of economic impact of the severe acute respiratory
syndrome (SARS) epidemic. SARS was trivial in size and scope compared
with even a modest flu pandemic.
UNITED STATES IS NOT ADEQUATELY PREPARED
Congress and the Administration have begun to realize the real
threat that influenza poses to the United States as evident by the
allocation of additional monies for influenza activities in recent
years. The Administration has proposed an additional $120 million for
influenza preparedness activities in the fiscal year 2006 budget to
further strengthen pandemic influenza preparedness efforts. While
welcome, this is a small investment. Additionally, the Department of
Health and Human Services (HHS) recently proposed a thoughtful and
scientifically based draft pandemic preparedness and response plan that
lays out public health measures to counter a sudden worldwide influenza
epidemic. IDSA has provided extensive comments on the plan and
currently is participating on an HHS workgroup to develop specific
policies and improve preparedness. CDC has worked to strengthen its
scientific and epidemiologic capacity to respond. The National
Institutes of Health (NIH) has begun efforts to develop vaccine for
avian influenza and has increased support for other basic research.
IDSA recognizes and appreciates the increasing level of federal
support for U.S. preparedness efforts. However, IDSA agrees with the
Institute of Medicine and virtually all experts who have concluded that
the United States is at present woefully unprepared to respond to the
next flu pandemic.
Two promising strategies can decrease the impact of a flu pandemic.
Vaccination is the primary strategy to prevent influenza during normal
years and during a pandemic. The recent shortage of flu vaccine
highlights the fragility of our nation's vaccine supply. We clearly
need a greater capacity to produce vaccine. This means we must attract
more vaccine manufacturers to produce influenza vaccine within our
borders. It has been estimated that vaccinating the U.S. population
against a pandemic flu strain might require 600 million doses of
vaccine (two doses for each person might be needed). Even in a normal
year, only 50 million to 60 million doses of vaccine can be
manufactured in the United States. Counting doses of vaccine imported
from abroad, about 90 million doses are used. In the best case, it will
take four to six months to begin to produce a pandemic influenza
vaccine. Unfortunately, only three influenza vaccine manufacturers
currently produce flu vaccines for the U.S. market; only one of them
produces its vaccine within the United States.
Antiviral drugs would be the only available agents for treatment
and prevention in the early phase of a pandemic. However, adequate
supplies will not be available unless decisive action is taken. Global
production of these agents is modest. If antivirals are to be available
in an emergency they would need to be stockpiled in advance.
Strengthening our pandemic influenza preparedness activities also
will provide significant benefits during the typical ``interpandemic''
flu season when 36,000 American lives are lost and 200,000 are
hospitalized each year. The same cannot be said for preparedness
activities for intentional biological emergencies such as smallpox,
which does not exist in nature, or anthrax, which is an extremely rare
disease.
POTENTIAL LEGISLATIVE AND ADMINISTRATIVE SOLUTIONS
Considering the significance of the threat, IDSA has identified the
following short and long term strategies to strengthen the U.S. level
of preparedness and response to both interpandemic and pandemic
influenza.
Secure vaccine and antiviral supplies.
Adequate supplies of antivirals and if possible vaccine, need to be
in place before a pandemic strikes, along with a plan to distribute
them. More must be done to bring additional manufacturers into the
vaccine business, particularly to develop domestic based companies so
that the United States is not dependent on foreign suppliers. Increased
use of vaccine during interpandemic years is needed to increase the
manufacturing capacity. Without this strengthened capacity, we will be
unable to meet the high demand that will occur during an influenza
pandemic.
Stockpiles of antiviral drugs are also essential. IDSA has proposed
a stockpile of antivirals sufficient to treat 50 percent of the U.S.
population. This stockpile will help to reduce mortality and allow
vital services such as medical care and emergency services to continue.
Clearly, the current stockpile, which could treat less than 2 percent
of the U.S. population, is inadequate. The cost of developing an
adequate stockpile cannot be paid for by shifting funds within HHS
agencies; it will require a separate appropriation. Given the enormous
burden of illness and death anticipated in a pandemic, however, this
investment promises an excellent return. In addition, the entire
production capacity for oseltamivir is located in Switzerland. As with
influenza vaccines, IDSA fully supports the development of antiviral
production capacities within the United States.
It is essential that we develop a specific strategy to distribute
antiviral drugs and vaccines to states, local health departments, and
points-of-care. We support the effort currently underway by the
Pandemic Influenza Working Group of the National Vaccine Advisory
Committee (NVAC) to provide detailed estimates of the priorities for
use of antivirals and the amount of drug needed to reach different
target groups. This will provide more precise estimates of the size and
cost of a stockpile needed to provide a specific level of benefit.
Advance Research and Development of Antivirals and Vaccines.
Current manufacturing of influenza vaccine depends on egg-based
technology that is 60 years old. It imposes limits on the ability to
ramp up production and to work with strains that are lethal to eggs.
Research and development of newer vaccines is vital. NIH has recently
outlined funding for work on cell-culture based vaccine and for
antigen-sparing approaches. These are vital efforts and should be
accelerated. Equal attention needs to be paid to our ability to rapidly
and safely license new technologies to produce new vaccines for
widespread use. Truly innovative vaccines could be developed that do
not need to be redesigned each year. Investment in this research could
be extremely important but will take many years to realize a benefit.
Research also is needed to develop new antivirals with anti-
influenza activity. We are currently dependent on a single agent,
oseltamavir (also known as Tamiflu, an antiviral produced by Roche
Pharmaceuticals). In the event H5N1 becomes a pandemic strain, this
vulnerability will be dangerous.
Create tax incentives for U.S. vaccine and antiviral manufacturers.
The United States does not have the manufacturing capacity to
produce enough vaccine and antivirals to meet its needs in a pandemic.
Tax credits should be offered to encourage companies to build new
manufacturing facilities in this country so that the United States is
not dependent on foreign suppliers. Tax incentives and patent
extensions should be available for companies that conduct research and
develop new anti-flu therapies.
Guarantee a market for influenza vaccines.
Most pharmaceutical companies have left the vaccine business
because demand is extremely unpredictable. Even last season, when there
was a severe shortage of vaccine, millions of doses of flu vaccine went
unused. To secure vaccine supplies for future influenza outbreaks, the
government needs to guarantee it will buy a set amount of vaccine each
season, and buy back a percentage of unsold vaccine at the end of each
season.
The Centers for Medicare and Medicaid Services (CMS) also has a
critical role to play. The recent increase in the Medicare
reimbursement for administration of flu vaccine, although long overdue,
was a positive step. However, the current system still places
physicians at financial risk, which may have consequences for patient
access to vaccine. Physicians must purchase vaccine annually in advance
of the flu season. Unused vaccine is then discarded at the end of the
flu season. Physicians are not compensated for the unused product,
which, of course, may make them less inclined to purchase vaccine in
advance in future years. As all Medicare beneficiaries should receive
annual influenza vaccine, CMS should consider how to purchase enough
vaccine for Medicare patients in a manner that does not place
physicians at risk.
Strengthen liability protection during emergency outbreak response.
In case of a declared influenza emergency, it will be vital to
immunize and treat large numbers of people. Even rare adverse reactions
following vaccination and treatment would become more common when
hundreds of millions are treated, and accelerated approval of new
vaccines and treatments might not uncover all rare adverse events.
Health care workers and medical facilities administering vaccines or
treatments, as well as the companies that make them, should be
protected from lawsuits stemming from adverse events so long as they
follow standard medical and manufacturing procedures. A compensation
fund similar in structure to the Vaccine Injury Compensation Fund
should be established to cover the medical costs and lost earnings of
anyone who develops complications due to vaccination or treatment.
Improve coordination, communication, and planning.
Many federal, state, and local agencies have vital roles in
preparedness, planning, and response. HHS should develop a detailed
plan to coordinate pandemic response at all levels, from local to
national to international, including links between federal authorities
and clinicians throughout the country. HHS should also define CDC as
the coordinating authority within the department. Moreover, there needs
to be a clear ability to coordinate efforts between departments,
including not only HHS, but also Defense, Agriculture (USDA), Homeland
Security, and State.
Require health care workers to be vaccinated.
Unfortunately, health care workers caring for sick people often
spread patients' infections. In 2002, only 36 percent of U.S. health
care workers received influenza vaccine. To improve patient safety,
prevent unnecessary deaths and disease, and provide an example to
patients, we believe that annual flu vaccination should be required for
all health care workers who have contact with patients, with options to
waive vaccination after signing an appropriate waiver.
Strengthen education.
Health care workers and the public need to better understand the
seriousness and potential impact of an influenza pandemic, as well as
how to prevent and treat it.
Commit to international pandemic preparedness.
A coordinated international effort is vital. The United States
should work with other countries, particularly those most vulnerable,
on plans to ensure that they have sufficient antiviral and vaccine
supplies to protect their populations.
Strengthen the response of federal agencies.
The Food and Drug Administration should ``fast-track'' vaccine and
antiviral review, and streamline regulation of the manufacturing
process. Congress should increase the CDC's budget for global
surveillance to detect influenza strains with pandemic potential. The
NIH budget also should be increased for research to identify and
evaluate new methods to accelerate vaccine research and development.
USDA should develop a plan for culling poultry or other livestock and
compensating farmers in the event of a pandemic, if necessary.
CONCLUSION
The United States remains unprepared for pandemic influenza that
could kill millions of Americans over a short period of time with
little warning. We may not have much time. The United States needs a
rational, integrated, and comprehensive plan that will ensure an
effective response. We also need a better-coordinated approach, both
domestically and globally. If IDSA's recommendations are implemented,
our nation will be better prepared for both the next pandemic and for
influenza outbreaks that occur every year. As Winston Churchill said:
``It is not enough to say, `We are doing our best.' You have got to
succeed in doing what is necessary.''
IDSA appreciates the opportunity to testify before the House Energy
and Commerce Health Subcommittee today. We look forward to working with
you in the coming months to develop federal legislation needed to
strengthen U.S. efforts to prepare for the next influenza pandemic.
Thank you. I will be happy to answer any questions.
Mr. Ferguson. You are definitely in the right room. Mr.
Hosbach.
STATEMENT OF PHILLIP HOSBACH
Mr. Hosbach. Mr. Chairman, members of the committee, I
would like to thank you for the opportunity to speak with you
today and more importantly, for holding this critically
important hearing.
Sanofi pasteur is committed to working with the Federal
Government to develop a safe and effective pandemic vaccine to
protect the American public. Today I would like to outline four
necessary steps to develop and administer a pandemic influenza
vaccine.
Sanofi pasteur is the world's largest influenza vaccine
manufacturer. We produce vaccines against more than 20
diseases. Worldwide we distribute almost one billion doses of
vaccine annually. Our U.S. operations are located in
Swiftwater, Pennsylvania where influenza vaccine has been
produced for more than 30 years. Approximately 95 percent of
that influenza vaccine that is made in Swiftwater is used
exclusively in the United States.
In the past decade sanofi pasteur has steadily increased
U.S. production of influenza vaccine. Last year we produced 58
million doses. We are in the final design stages of our
influenza vaccine facility expansion and we also recently
invested in a new expanded filling and packaging facility. Both
of these projects will significantly expand our U.S. influenza
vaccine production and capacity.
As most of you know, vaccines by their very nature are
challenging to develop, produce, and distribute. We believe the
expertise of vaccine manufacturers, particularly those with a
track record in influenza vaccine production and distribution
should be utilized early in the planning process.
The enormous public health threat posed by a pandemic
prompted sanofi pasteur to take specific steps for a
comprehensive pandemic strategy, including the formation of a
global working group to examine preparedness, production,
distribution, and communication issues. We have cooperated with
HHS exchanging ideas on how best to prepare for and respond to
a pandemic.
In addition, we entered into several contracts with the
Federal Government. We received two H5N1 pandemic influenza
vaccine contracts, as mentioned by Dr. Fauci. In accordance
with these agreements, we delivered 8,000 investigational doses
of H5N1 vaccine to NIH for the clinical trials that have
already started. We also produced two million H5N1 bulk doses
at large scale.
Sanofi pasteur also received a contract to establish and
maintain flocks of egg-laying hens on a year-round basis. As
you know, eggs are utilized early in the stages of vaccine
production, and prior to this agreement, were only available on
a seasonal basis. Finally, sanofi pasteur was awarded a
contract to speed development of a cell culture influenza
vaccine in the United States.
Mr. Chairman, we are encouraged by the increased attention
pandemic planning is receiving from the government, industry,
international agencies, and key stakeholders. However, the
failure to address critical challenges could aversely affect
our ability to respond to a pandemic. I would like to outline
four steps necessary to develop and administer a pandemic
influenza vaccine.
First, we need to steadily increase inter-pandemic
immunization rates. Manufacturers will produce additional
vaccine to meet predicatble demand. Steady and sustained
increase in inter-pandemic demand will give manufacturers the
confidence to continue expansion plans and new companies an
incentive to enter the marketplace. To achieve this all key
stakeholders need to work together to encourage higher
influenza immunization rates. As a Nation, we have never
immunized more than 85 million people in any given year. We can
and must do better.
Second, we need to ensure proper combination of private and
public sector distribution of a vaccine in a pandemic. While it
will be important to establish mechanisms for mass
immunizations in public clinics, private physicians' offices
will also play a key role in a pandemic. During a typical
influenza season, the private sector distributes over 85
percent of the Nation's supply. The private market itself
provides maximum flexibility in vaccine distribution.
Last year's influenza vaccine shortage illustrated sanofi
pasteur's unique expertise in shipping product to any U.S.
location within 24 to 48 hours. We ship vaccines to any users
in accordance with the CDC's recommendations and distribution
plan. Our unprecedented collaboration with the CDC underscores
our commitment to America's public health.
Third, vaccine liability protection is another critical
issue in pandemic preparedness. A special compensation
liability protection program will need to be established
similar to the 1976 Swine Flu and 2002 small pox models. The
pandemic liability program should be distinct and separate from
the existing Vaccine Injury Compensation Program and should
focus exclusively on a monovalent influenza vaccine. Failure to
offer liability protection could have profound implications for
the development, testing, and subsequent licensure and
administration of doses of vaccine. It is important to address
liability before a health emergency arises. We urge Congress to
establish liability protections as strong as those afforded
providers of small pox vaccine under the Homeland Security Act
of 2002. Strong and effective vaccine liability provisions
ensure that manufacturers can bring a pandemic vaccine to
market as quickly as possible.
Finally, CDC must continue to build a pediatric vaccine
stockpile. I think many of the members of the panel have
already spoken about that. Let me reiterate, when an influenza
pandemic strikes the United States, sanofi pasteur will have to
shift personnel and other resources away from routine vaccine
production to optimize production of a monovalent pandemic
influenza vaccine. Congress has appropriated funds to establish
stockpiles of routine childhood vaccines to be used in case of
a disruption in supply, but most funds remain unused. And I
won't go into any further detail because I think we have
further details there.
But finally, sanofi pasteur is committed to protecting
America's public health in the fight against influenza through
immunization. We want to commend Congress and the
administration for dedicating time and resources to this
critical area. Thank you.
[The prepared statement of Phillip Hosbach follows:]
Prepared Statement of Philip Hosbach, Vice President, Immunization
Policy and Government Affairs, Sanofi Pasteur
On behalf of sanofi pasteur, thank you for the opportunity to
testify today before the Energy and Commerce Subcommittee on Health.
Sanofi pasteur is committed to working with the federal government to
develop a safe and effective vaccine to protect the American public in
the event of an influenza pandemic. Our common goal is to provide
sufficient vaccine for 300 million Americans within the first 12- to
18-month period of a pandemic, and we welcome the chance to provide the
committee with our perspective on this important public health issue.
Sanofi pasteur, the world's largest influenza vaccine manufacturer,
also manufactures vaccines against more than 20 different diseases.
Worldwide, we produce almost 1 billion doses of vaccines annually. The
company, which employs more than 9,000 employees worldwide, is
headquartered in Lyon, France. Sanofi pasteur's US operations are
located in the Pocono Mountains in Swiftwater, Pa., at a site where
vaccine has been produced for more than 100 years. Influenza vaccine
has been produced in this facility for more than 30 years and 95% of
this vaccine is used exclusively to supply the United States. Sanofi
pasteur also has an influenza vaccine production facility in France
that supplies other markets.
During the past decade, sanofi pasteur has reliably and
consistently increased production of influenza vaccine in the US. Last
year, we produced 58 million doses for the US market. We continue to
expand our vaccine manufacturing capacity in Pennsylvania and have
embarked on the largest infrastructure investment in the company's
history, spending almost $80 million to build a new formulation and
filling facility. We are also in the final design phases of our
influenza vaccine facility expansion, which will significantly increase
our US production capabilities.
PANDEMIC OVERVIEW
An influenza pandemic is a global epidemic that has the potential
for severe morbidity and mortality.
Three influenza pandemics occurred during the 20th century: the
1918-1919 Spanish flu pandemic, the 1957 Asian flu pandemic and the
1968 Hong Kong flu pandemic. The Spanish flu pandemic was the most
severe, causing over 500,000 deaths in the US and an estimated 20 to 40
million deaths worldwide.
The prospect of a pandemic is taking on increasing urgency because
of the emergence of an H5N1 avian influenza strain in Southeast Asia 17
months ago. It continues to circulate and has the potential to mutate
and become a human pandemic strain. To date, it has infected at least
97 people and killed more than half of its victims.1 This is
a completely new strain and epidemiologists believe the American
population would be at risk if it spreads between humans.
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\1\ Remarks to the 58th World Health Assembly Plenary Session, Mike
Leavitt. U.S. Department of Health and Human Services. Numbers updated
on 5/23/05. Accessed May 17, 2005 at: http://www.hhs.gov/news/speech/
2005/050516.html
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Many experts believe that if this H5N1 virus sparks the next
pandemic, it would most closely resemble the 1918 pandemic in terms of
morbidity and mortality.2
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\2\ Osterholm MT. Preparing for the next pandemic. N Engl J Med.
2005 May 5;352(18):1839-42
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According to the World Health Organization (WHO), the next pandemic
is likely to result in 1 to 2.3 million hospitalizations and 280,000 to
650,000 deaths in industrialized nations alone. The US Centers for
Disease Control and Prevention (CDC) estimated that as many as 207,000
Americans could die and up to 734,000 could be hospitalized during the
next pandemic. Other estimates are even higher. Studies have estimated
the costs of an influenza pandemic in the US between $71 billion and
$166.5 billion. These estimates include only direct costs of medical
care and indirect costs of lost productivity and mortality rates. Some
experts have predicted that a major pandemic could bring the global
economy to a halt.3
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\3\ Osterholm MT. Preparing for the next pandemic. N Engl J Med.
2005 May 5;352(18):1839-42
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Sanofi pasteur recognizes the urgency of adequate preparation for a
pandemic event and is taking steps to be ready.
PROGRESS TO DATE
We believe the expertise of vaccine manufacturers, particularly
those with a track record in influenza vaccine production and
distribution, should be utilized early in the planning process.
Vaccines, by their very nature, are challenging to develop, produce and
distribute. Manufacturers have a unique understanding of these
challenges and can provide valuable process and policy input. Our
knowledge and experience with the complexities of vaccine supply make
industry an essential partner in pandemic planning and policy
formulation.
The enormous public health threat posed by a potential pandemic
prompted sanofi pasteur to re-examine our internal pandemic planning
process. We have taken specific and deliberate steps toward a
comprehensive pandemic strategy. We formed a global working group to
examine preparedness, development, communications and legal issues. In
the US, we have worked in cooperation with the US Department of Health
and Human Services (HHS) to exchange ideas on how best to prepare for
and respond to a pandemic influenza outbreak, and have provided
significant input into the initial draft of its pandemic plan.
We have moved forward with clinical research and vaccine production
because of important funding provided by Congress and the
Administration. In May 2004, sanofi pasteur entered into the first of
four pandemic agreements with the US government. The National Institute
of Allergy and Infectious Diseases (NIAID) contracted with us to
produce an investigational influenza vaccine based on the currently
circulating H5N1 avian influenza virus strain. On March 10, 2005, in
accordance with that agreement, sanofi pasteur delivered more than
8,000 investigational doses, which currently are being used in NIH-
conducted clinical trials.
In September 2004, the company was awarded a second contract by HHS
to produce two million bulk doses of an attenuated version of the same
H5N1 avian influenza virus strain of vaccine. This contract represents
an important step in gaining experience producing pandemic influenza
vaccine on a large scale. This is critical because scale-up presents
unique challenges in vaccine production. Part of our agreement is to
determine the stability of this vaccine, which is important for
understanding our ability to establish an H5N1 reserve.
Sanofi pasteur subsequently entered into a third agreement with HHS
to establish and maintain flocks of egg-laying hens and to maintain
other essential supplies. The goal is to ensure our ability to
manufacture pandemic influenza vaccine at current full capacity levels
on a year-round basis. Until now, egg availability has existed only on
a seasonal basis to support normal influenza vaccine production. The
agreement also calls for sanofi pasteur to manufacture, on an annual
basis, investigational influenza vaccine of a candidate pandemic-like
strain. Each year, HHS will identify the strain to be used in the
investigational lot and will provide the reference virus on which each
investigational lot will be based. This will enable us to gain
experience working with various viral strains that might be similar to
the next pandemic strain.
Finally, in April 2005, sanofi pasteur was awarded a fourth
contract from HHS. This was to speed the development process for new
cell culture influenza vaccines in the US and to design a US-based cell
culture influenza vaccine manufacturing facility.
Required Action:
We are encouraged by the increased attention pandemic planning is
receiving from the US government, industry, international agencies and
key stakeholders. However, unresolved critical issues remain. The
failure to address these challenges could adversely affect our
country's ability to respond to a pandemic event.
I would like to briefly outline steps that should be taken to help
the country better prepare for a pandemic and minimize the effects
should one occur.
A first step is to steadily increase interpandemic influenza
immunization rates. Manufacturers will respond to increased and
predictable demand by producing additional vaccine to fulfill this
demand.
This is important because our ability to produce and administer
large quantities of influenza vaccine during interpandemic periods will
enable a more rapid response during a pandemic. Increasing capacity in
dedicated influenza vaccine production facilities and establishing an
infrastructure that can deliver vaccine and immunize large numbers of
people in a short period of time is a key component of pandemic
preparedness.
To that end, Congress, industry and stakeholders need to work
together to encourage higher influenza immunization rates in accordance
with HHS' Healthy People 2010 immunization goals. The objective is to
immunize approximately 180 million Americans. However, as a nation, we
have never immunized more than 85 million people in any given year.
This is unacceptable. A steady and sustained increase in interpandemic
demand would give current manufacturers the confidence to continue
expansion plans and new companies the incentive to enter the market.
Second, we need to ensure a proper combination of private and
public sector distribution of vaccine in the event of a pandemic. We
believe that while it will be important to establish mechanisms for
mass immunizations and clinics, the private physicians' offices will
continue to play a vital role as well. During a typical influenza
season, the private sector distributes more than 85% of the nation's
influenza supply. The private market provides maximum flexibility in
vaccine distribution and allows us to reach large segments of the US
population in their ``medical homes.'' This includes the elderly, who
should not stand in long lines and may be more comfortable with their
personal physicians.
Last year's influenza vaccine shortage illustrated sanofi pasteur's
unique expertise in processing and shipping product to virtually any
location in the United States within 24-48 hours. We shipped vaccines
to end-users in accordance with the CDC's recommendations and
distribution plan. Further, the unprecedented degree of collaboration
between sanofi pasteur and the CDC underscores our willingness to work
with public agencies to protect America's public health. This year,
sanofi pasteur has modified our ordering process to provide that, in
the event of another shortage, available vaccine reaches high-risk
people first. All of our ``pre-book'' customers are being asked to
estimate what percentage of the vaccine they are requesting will be
used for priority patients. The systems utilized to collect these data
and the ability to easily identify priority recipients, as specified by
federal, state and local governments, will be key in protecting the
public health in the event of a pandemic. We also believe that there
should be greater funding for coordinating communications between
federal and state agencies and the private sector regarding vaccine
allocation issues.
A third challenge is to continue to build pediatric stockpiles of
all routinely recommended pediatric vaccines. When pandemic influenza
strikes the United States, sanofi pasteur will have to slow down
routine production, filling, and packaging for all other vaccines. We
would have to shift personnel and other resources to optimize
production and release of a monovalent pandemic influenza vaccine.
Thus, it is essential that we resolve problems associated with the
pediatric vaccine stockpile. HHS has appropriated funds but they have
not been spent.
You may have read The Washington Post article on April 17, 2005
entitled ``Pediatric Vaccine Stockpile at Risk.'' It pointed out that
only 13 million of the requested 41 million doses of pediatric vaccine
have been stockpiled due to a Securities and Exchange Commission rule
that clarified standard accounting practices for a bill and hold sale.
As a result, what had been a 20-year routine practice of stockpiling
vaccines is no longer an option for sanofi pasteur. Over the last two
years, we have been actively engaged in discussions with the CDC to
address the issue. We encourage the Committee to help resolve the
issues that surround the establishment of routine pediatric stockpiles
in advance of a pandemic.
Pandemic influenza vaccine liability protection is another critical
issue in pandemic preparedness. A special compensation and liability
protection program will need to be established similar to the 1976
swine flu and 2002 smallpox model. Liability protection for companies
is essential to ensure that manufacturers are able to fully participate
in the development and licensure of a pandemic vaccine. This is of
paramount importance. The new program should be completely distinct and
separate from the existing Vaccine Injury Compensation Program (VICP).
It should focus exclusively on liability protection for a monovalent
influenza pandemic vaccine, precisely the type of vaccine that will be
produced in a pandemic event. The failure to offer liability protection
on a timely basis could have profound implications for the actual
testing and development of large-scale production of vaccine, leaving
the nation unprepared. It is important to address liability issues
before a health emergency arises. This ensures that pandemic vaccines
will be developed, economic costs will be mitigated, and the potential
for needless and costly litigation will be curtailed.
We strongly urge Congress to consider--and establish--liability
protections that are as strong as those afforded providers of smallpox
vaccine under the Homeland Security Act of 2002. Vaccine liability
provisions ensure that we can bring a pandemic influenza vaccine to
market as quickly as possible.
Sanofi pasteur is committed to protecting America's public health
in the fight against influenza through vaccinations. We want to commend
Congress and the Administration for dedicating time and resources to
this critical area. Thank you for giving us the opportunity to express
our views on this important issue.
Mr. Ferguson. Thank you very much. Dr. Iacuzio.
STATEMENT OF DOMINICK A. IACUZIO
Mr. Iacuzio. Mr. Chairman and the members of the
subcommittee, I am Dr. Dominick Iacuzio, Medical Director for
Tamiflu at Hoffmann-La Roche, a research-based pharmaceutical
company. Prior to joining Roche, I worked at the NIH National
Institute of Allergy and Infectious Diseases where I served as
the Respiratory Diseases Branch Principal Technical Advisor for
the Influenza Program. I am grateful for this opportunity to
discuss the role of antiviral drugs and pandemic influenza
preparedness and response, and I request that my full written
testimony be submitted for the record.
As you have heard from the other witnesses today, pandemic
influenza is one of our greatest public health threats.
According to the Department of Homeland Security, a potential
consequence for even a limited influenza pandemic could result
in economic disruption, hospitalizations, and deaths far in
excess of most terror attack scenarios.
Efforts to prepare for the pandemic threat cannot rely on
vaccines alone. It is widely recognized that antiviral drug
stockpiling is an important component of pandemic influenza
preparedness. The Infectious Diseases Society of America has
recommended, as you heard this morning, that the U.S. stockpile
enough antiviral, up to 50 percent of the U.S. population.
Roche's Tamiflu is the leading prescription oral antiviral
drug for influenza. Tamiflu was approved by the Food and Drug
Administration in 1999 for treatment of Type A and B influenza
and in 2000 for influenza prophylaxis or prevention.
Fortunately, Tamiflu is well-tolerated with nausea and vomiting
being most frequently reported as the adverse events. The
efficacy of Tamiflu against Avian Influenza has been
demonstrated by leading researchers and animal studies, in
vitro data, and practical experience during the 2003 Avian
Influenza outbreak in the Netherlands of H7N7. According to the
World Health Organization, they have recommended use of Tamiflu
to control the Avian Flu outbreaks in Asia.
Although the potential for resistance must be monitored
carefully, no transmission of a Tamiflu-resistant virus in
humans has been detected to date. It is imperative that Tamiflu
be stockpiled in advance of a pandemic since inherent
complexities in production severely limit our capability, our
ability, to rapidly meet large-scale, unanticipated demand. The
manufacturing process for Tamiflu takes 8 to 12 months from raw
materials to finished product. The process involves many inputs
and steps, including a unique starting material and a
potentially explosive production step that can be carried out
only in specialized and very costly facilities.
Historically, Roche has not produced the levels of Tamiflu
required for global stockpiling. However, since 2003 we have
increased total Tamiflu production capacity nearly eight-fold.
Most importantly, early in our discussion HHS made several
requests to Roche, all of which have been fulfilled. First,
Roche has developed a U.S.-based supply chain. Second, Roche
developed special U.S. packaging for stockpiled Tamiflu in
order to extend dating and ease distribution and
administration. Roche undertook these efforts in good faith and
at great economic risk.
Roche is also developing a synthetic process for
manufacturing the chemical used in the initial production step.
This will ultimately reduce reliance on natural sources. Roche
has received and is filing on schedule pandemic stockpile
orders for Tamiflu from 25 countries worldwide. Discussions are
underway for the U.S. Government to purchase significantly
greater amounts of Tamiflu. However, HHS stockpile purchases to
date are sufficient to treat less than 1 percent of the U.S.
population. We have also received a non-bonding letter of
intent for HHS to purchase additional treatments to cover under
2 percent of the population.
In contrast, countries such as the United Kingdom, France,
Finland, Norway, Switzerland, and New Zealand are ordering
enough Tamiflu to cover between 20 and 40 percent of their
populations. Unfortunately, given the complexities I have
described, the increasing global demand, any government that
does not stockpile sufficient quantities of Tamiflu in advance
cannot be assured of an adequate supply at the outbreak of an
influenza pandemic.
If I can leave you with three messages from my testimony
today, they are the following: first, there is a consensus by
global health authorities that Tamiflu is effective and an
important tool in pandemic influenza preparedness and response;
second, that other nations are currently well ahead of the
United States in Tamiflu stockpiling; and finally, the U.S. has
to make commitment now to ensure a timely and adequate supply
of Tamiflu. We at Roche want to continue to work closely with
the subcommittee and HHS to assist the U.S. in ensuring
pandemic preparedness. On behalf of Roche, thank you for
highlighting this critical issue, and I will be pleased to
answer any questions that you may have.
[The prepared statement of Dominick A. Iacuzio follows:]
Prepared Statement of Dominick A. Iacuzio, Medical Director, Hoffmann-
La Roche Inc.
Mr. Chairman and Members of the Subcommittee, I am Dr. Dominick
Iacuzio, Medical Director at Hoffmann-La Roche Inc. (``che''), a
research-based pharmaceutical company. Since joining Roche, I have been
the medical officer responsible for Tamiflu ' (oseltamivir
phosphate), the world's first oral medication effective against the
type A and B strains of the influenza virus. Prior to joining Roche, I
worked at the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, where I served as the Respiratory
Disease Branch's principal technical advisor for the Influenza Program.
I am grateful for this opportunity to discuss with you the role of
antiviral drugs in pandemic influenza preparedness and response, and I
commend the Subcommittee for its efforts to protect the American people
against this very real public health threat.
THE PANDEMIC INFLUENZA THREAT
Every year, seasonal influenza causes an average of 36,000 deaths
and 114,000 hospitalizations.1 In addition to the annual
influenza seasons, three influenza pandemics took place during the 20th
century. In 1918, approximately 500,000 people died from the so-called
``Spanish Flu,'' and up to 50 million may have died worldwide. The
1957-58 ``Asian flu'' killed 70,000 Americans, and the 1968-69 ``Hong
Kong flu'' caused over 34,000 deaths in this country.2
---------------------------------------------------------------------------
\1\ Department of Health and Human Services, Draft Pandemic
Influenza Response and Preparedness Plan, Core Document, 14 (Aug.
2004), available at http://www.hhs.gov/nvpo/pandemicplan/
finalpandemiccore.pdf.
\2\ Centers for Disease Control and Prevention, Fact Sheet:
Information About Influenza Pandemics (March 8, 2005).
---------------------------------------------------------------------------
An influenza pandemic occurs when an existing influenza strain
mutates. The emergence of such a new viral strain, the lack of previous
exposure and immunity to the virus, and the lack of a vaccine that can
protect against the new strain can ignite a global influenza epidemic,
i.e., a pandemic. It has been 36 years since the last influenza
pandemic, thanks in large part to the development of influenza
vaccinations, as well as methods to predict influenza strains and
redesign vaccines annually to include the strains predicted to affect
the population in a given year.
However, it appears that the factors associated with a pandemic are
now moving into place. First, we have a highly pathogenic strain of
avian influenza circulating widely in Asia. Second, this avian strain
appears to be increasingly capable of causing deadly disease in humans
and animals. In fact, the avian virus has been fatal in approximately
60 percent of people infected by it.3 While efficient human-
to-human transmission of the virus--the final barrier to an influenza
pandemic--has yet to occur, it is possible--if not probable--that
persons harboring both human and avian influenza viruses could become
``mixing vessels'' from which a new virus emerges that is easily
transmitted among humans. Indeed, a recent World Health Organization
(WHO) assessment noted that new epidemiological findings in Asia
indicate that the virus may be becoming more capable of human-to-human
transmission.4
---------------------------------------------------------------------------
\3\ World Health Organization, Cumulative Number of Confirmed Human
Cases of Avian Influenza A/(H5N1) Reported to WHO (May 19, 2005),
available at http://www.who.int/csr/disease/avian_influenza/country/
cases_table_2005_05_19/en/print.html.
\4\ World Health Organization, Inter-country Consultation,
Influenza A/H5N1 in Humans in Asia (May 6-7, 2005).
---------------------------------------------------------------------------
Make no mistake: should an influenza pandemic occur, the threat to
the U.S. public would be great. In its draft Pandemic Influenza
Preparedness and Response Plan (Plan), the U.S. Department of Health
and Human Services (HHS) recognizes an influenza pandemic as having ``a
greater potential to cause rapid increases in death and illness than
virtually any other natural health threat.5 Health experts
estimate that if the virus is passed efficiently between humans, avian
flu could result in a pandemic causing over 50 million deaths
worldwide.6 Studies cited recently by the Centers for
Disease Control and Prevention (CDC) estimate that, without vaccines or
drugs, a ``medium level'' pandemic would kill between 89,000 and
207,000 Americans, and sicken another 20 to 47 million--causing up to
42 million outpatient visits and 734,000 hospitalizations.7
In fact, according to the Department of Homeland Security, the
potential consequences of even a limited influenza pandemic could
result in deaths, hospitalizations and economic disruption far in
excess of most terror attack scenarios.8 In addition to the
human toll, the economic cost of such a pandemic has been estimated at
$71 to $167 billion.9 Without a doubt, planning for such a
global health crisis must be a major public health priority.
---------------------------------------------------------------------------
\5\ Department of Health and Human Services, Draft Pandemic
Influenza Response and Preparedness Plan, Executive Summary 3, (Aug.
2004), available at http://www.hhs.gov/nvpo/pandemicplan.
\6\ World Health Organization, Estimating the Impact of the Next
Influenza Pandemic: Enhancing Preparedness (Dec. 8, 2004), available at
http://www.who.int/csr/disease/influenza/preparedness2004_12_08/en/
index.html.
\7\ Centers for Disease Control and Prevention, Influenza Pandemic
Fact Sheet (Mar. 8, 2005), available at http://www.cdc.gov/flu/avian/
gen-info/pandemics.htm.
\8\ 15 Nightmares for Disaster Planning, N.Y. Times (March 16,
2005).
\9\ CDC, Influenza Pandemic Fact Sheet.
---------------------------------------------------------------------------
Both the HHS Plan and the WHO Global Influenza Preparedness Plan
emphasize that adequately addressing the threat of a pandemic influenza
outbreak will require availability of both an influenza vaccine and
antiviral drugs.10 If available, vaccines, which typically
are administered before an outbreak of influenza, can provide an
effective defense against developing seasonal or pandemic influenza, as
well as in slowing transmission among humans.
---------------------------------------------------------------------------
\10\ Department of Health and Human Services, Draft Pandemic
Influenza Response and Preparedness Plan, Core Document 23 (Aug. 2004),
available at http://www.hhs.gov/nvpo/pandemicplan/
finalpandemiccore.pdf; World Health Organization, WHO Global Influenza
Preparedness Plan 13 (2005), available at http://www.who.int/csr/
resources/publications /influenza/WHO_CDS_CSR_GIP_2005_5.pdf.
---------------------------------------------------------------------------
However, vaccines have important limitations. First, accurately
predicting the specific viral strain or strains that ultimately may
cause an influenza pandemic cannot be assured. Consequently, effective
vaccines may not be available at the time a pandemic outbreak is first
detected. Second, the propensity of viruses to mutate can lead to the
rapid generation of new strains. Thus, there is a possibility that a
vaccine effective against the viral strain accountable for the outbreak
may be impotent against the virus' mutated progeny. This is one reason
why unique vaccines to guard against seasonal influenza must be
produced, licensed, and distributed each year, and thus, cannot be
stockpiled for use against multiple outbreaks. Finally, given the pace
of an outbreak of pandemic influenza, initial reliance on vaccines may
not be feasible. For example, the WHO estimates it will take six to
nine months to develop a vaccine effective against the circulating
pandemic virus strain.11 Of course, producing and
distributing the vaccine on a large scale also will take considerable
time, and a vaccine, once administered, may take several weeks to
trigger immunity, or require multiple administrations.
---------------------------------------------------------------------------
\11\ World Health Organization (WHO) Global Influenza Preparedness
Plan: The Role of WHO and Recommendations for National Measures Before
and During Pandemics (Apr. 2005), available at http://www.who.int/ csr/
resources/publications/influenza/WHO_CDS_CSR_EDC_99_
1/en/print.html.
---------------------------------------------------------------------------
For all of these reasons, HHS and the WHO have recommended that
efforts to prepare for an influenza pandemic not rely on vaccines
alone. As stated in a recent WHO report, ``[p]ending the availability
of vaccines, antiviral agents will be the principal medical
intervention for reducing morbidity and mortality, which becomes the
most important priority once a pandemic is underway.12
Notably, certain antiviral drugs can be used either to treat the flu or
as a prophylactic to prevent those at risk from becoming infected.
Recently published models suggest that an influenza pandemic could be
contained if 80 percent of those exposed to the virus used targeted
antiviral drugs prophylactically.13
---------------------------------------------------------------------------
\12\ World Health Organization, Avian Influenza: Assessing the
Pandemic Threat (Jan. 2005), available at http://www.who.int/csr/
disease/influenza/H5N1-9reduit.pdf.
\13\ N.M. Ferguson et al., A Population-Dynamic Model for
Evaluating the Potential Spread of Drug-Resistant Influenza Virus
Infections During Community-Based Use of Antivirals, 51 Journal of
Antimicrobial Chemotherapy 977 (2003); I.M. Longini et al., Containing
Pandemic Influenza with Antiviral Agents, 159 Am. J. Epidemiology 623
(2004).
---------------------------------------------------------------------------
Finally, antivirals have four additional characteristics that
warrant their inclusion in any influenza pandemic plan: (1) antivirals
have a long shelf-life, permitting them to be stockpiled for several
years, and thus immediately available when an outbreak occurs; (2)
antiviral drugs begin to work immediately after they are administered;
(3) certain antivirals work against multiple types of influenza; and
(4) utilization of antivirals does not interfere with immunologic
response.
THE ROLE OF TAMIFLU ' IN AN INFLUENZA PANDEMIC
Roche's Tamiflu ' (oseltamivir phosphate) is the leading
prescription oral antiviral drug. Tamiflu ' was approved by
the Food and Drug Administration (FDA) in 1999 for the treatment of
type A and B influenza. Specifically, Tamiflu ', a
neuraminidase inhibitor, works by attacking the influenza virus and its
ability to replicate, rather than simply addressing influenza symptoms.
Tamiflu ' is indicated for treatment of patients one year
and older, and, if taken within forty-eight hours of the onset of
symptoms, can help patients recover from the flu faster. As a
prophylactic, an indication approved in 2000, Tamiflu ' is
labeled for use by adults and adolescents 13 years of age and older,
although data on children one year of age and older have recently been
submitted to FDA for review. Tamiflu ' has a low likelihood
of clinically significant drug interactions and is generally well-
tolerated, with nausea and vomiting being the most frequently reported
adverse events. Tamiflu ' is available in both capsule and
pediatric suspension form.
As CDC Director Dr. Julie Gerberding informed this Subcommittee in
a November 2004 hearing, Tamiflu ' ``is the only antiviral
drug known to be effective against avian influenza.14 The
efficacy of Tamiflu ' against avian influenza has been
demonstrated in animal studies by leading researchers, in vitro data,
and practical experience during an avian influenza outbreak in the
Netherlands.15 Accordingly, the WHO has recommended use of
Tamiflu ' in those potentially exposed to avian flu in
Asia.16 Additionally, while a possibility exists for an
influenza virus to emerge with decreased sensitivity to any antiviral
drug, the Tamiflu '-resistant viruses isolated in humans to
date do not appear to be effectively transmissible.17
---------------------------------------------------------------------------
\14\ Flu Vaccine and Protecting High-Risk Individuals: Hearing
Before the Subcomm. on Health of the House Comm. on Energy & Commerce
108th Cong. (Nov. 18, 2004) (Statement of Dr. Julie Gerberding).
\15\ I.A. Leneva et al., The Neuraminidase Inhibitor GS4104
(Oseltamivir Phosphate) is Efficacious Against A/Hong Kong/156/97
(H5N1) and A/Hong Kong/1074/99 (H9N2) Influenza Viruses, 48 Antiviral
Res 101 (2000).
\16\ World Health Organization, WHO Interim Guidelines for Health
Monitoring of Persons Involved in Culling of Animals Potentially
Infected with Highly Pathogenic Avian Influenza Viruses (Mar. 22,
2004), available at http://www.wpro.who.int/avian_flu/docs/Health_
monitor_person.asp.
\17\ Data collected from patients treated with Tamiflu
', at its approved dose and for the approved treatment
duration, demonstrate an overall incidence of resistant virus of only
0.4 percent in adults and four percent in children aged one to 12. All
of the resistant virus strains were found unlikely to spread within a
community, even under conditions of widespread Tamiflu ' use
for both treatment and prevention of influenza. N. Roberts, Treatment
of Influenza with Neuraminidase Inhibitors: Virological Implications,
356 Philosophical Transactions of the Royal Society 1895 (2001).
---------------------------------------------------------------------------
For the prevention of influenza in those 13 years or older, Tamiflu
' is administered following close contact with an infected
individual who demonstrates characteristic symptoms of influenza, and
based on knowledge that influenza is circulating in the area for 10
days, or up to six weeks for seasonal prophylaxis. The approved dose
and duration of treatment--75mg twice daily for five days--is expected
to represent the minimum required for the management of an influenza
pandemic. To ensure Tamiflu ' remains effective against the
influenza virus, Roche does not recommend strategies which may utilize
lower doses or shorter duration of therapy compared with the
recommended dose.
ALTHOUGH ROCHE IS TAKING STEPS TO INCREASE TAMIFLU '
PRODUCTION, THE U.S. GOVERNMENT MUST MAKE CONTRACTUAL STOCKPILE
COMMITMENTS TO ENSURE A ROBUST U.S. ANTIVIRAL DRUG SUPPLY
As noted, both HHS and the WHO include stockpiling of antiviral
drugs as a central component of their developing plans for influenza
pandemic preparedness. Both the Infectious Diseases Society of America
(IDSA) and the WHO have recently acknowledged that Tamiflu
', in particular, is uniquely suited to pandemic
stockpiling, for several reasons: (1) its efficacy against influenza
types A and B; (2) the absence of a known Tamiflu '-
resistant virus transmissible in humans; and (3) the product's five-
year shelf life.
It is imperative that Tamiflu ' be stockpiled in advance
of the outbreak of a pandemic because inherent complexities in
production severely limit capacity to rapidly meet large-scale,
unanticipated demand. The manufacturing process for Tamiflu
' is complex, and takes 8-12 months from raw materials to
finished product. The process involves many intermediate steps,
including a unique starting material, and a potentially explosive
production step that can be carried out only in specialized and costly
facilities. Given these complexities, significant lead time is needed
to increase production capacity and build stockpiles of the quantity
required for an influenza pandemic.
Historically, Roche has produced enough Tamiflu ' to
meet the seasonal influenza demand. For example, just over one million
prescriptions for Tamiflu ' were written in 2003 in the
United States, while preceding years averaged 600,000 to 700,000
prescriptions. In contrast, the IDSA has recommended that the
government stockpile enough antiviral drugs to treat up to 50 percent
of the U.S. population.18
---------------------------------------------------------------------------
\18\ World Health Organization, Governments in a Dilemma Over Bird
Flu: Uncertainty Over the Risk Posed by Bird Flu to Human Health Has
Left Policymakers in a Dilemma (May 1, 2005), available at http://
www.who.int/bulletin/volumes/83/5/infocus0505/en/index1.html;
Infectious Diseases Society of America IDSA's Principles For Action
Needed to Prepare the U.S. to Effectively Respond to Interpandemic/
Pandemic Influenza (Mar. 10, 2005), available at http://
www.idsociety.org/Template.cfm?Section=Search &
CONTENTID=10445&TEMPLATE=/Content
Management/ContentDisplay.cfm.
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Despite the obstacles I have described, the company doubled
production capacity at our European facility from 2003 to 2004, and we
are doing so again during 2005. Roche plans additional expansion of
production capacity for Tamiflu ' in 2006. Most importantly,
early in our discussions HHS made several requests to Roche, all of
which we have fulfilled. First, Roche has developed a U.S.-based supply
chain. When that supply chain is launched later this year, total
Tamiflu ' active pharmaceutical ingredient and capsule
production capacity will have increased globally by nearly eight-fold
over production capacity in 2003. Second, Roche developed special U.S.
packaging for stockpiled Tamiflu in order to extend dating and ease
distribution and administration. Roche undertook these efforts in good
faith and at great economic risk. Moreover, Roche is developing a
synthetic process for manufacturing the chemical used in the initial
production step, which will ultimately reduce reliance on natural
sources.
Roche has received and is filling--on schedule--pandemic stockpile
orders for Tamiflu ' from 25 countries worldwide.
Discussions are underway for the U.S. government to purchase for its
stockpile significantly greater amounts of Tamiflu ' for
this year and beyond. However, HHS stockpile purchases to date total
approximately 2.3 million courses of treatment, or enough to treat less
than one percent of the U.S. population. We have also received a non-
binding letter of intent for HHS to purchase an additional three
million courses of treatment, or enough to cover under two percent of
the population. In contrast, countries such as the United Kingdom,
France, Finland, Norway, Switzerland and New Zealand are ordering
enough Tamiflu ' to cover between 20 to 40 percent of their
populations.
Unfortunately, given the complexities I have described, any
government that does not stockpile sufficient quantities of Tamiflu
' in advance cannot be assured an adequate supply at the
outbreak of an influenza pandemic. We are greatly concerned that with
the continually increasing global demand for Tamiflu ', and
in the absence of a long-term U.S. commitment to stockpile the product,
U.S.-manufactured Tamiflu ' may have to be exported to
countries with committed orders. While Roche commends HHS for its
efforts to date, we cannot emphasize enough the immediate need for the
United States government to make the contractual commitments necessary
to ensure that an adequate stockpile is developed to meet the looming
pandemic threat.
Alerted to the pandemic threat, governments now have an
unprecedented opportunity to attempt to minimize the catastrophic loss
of life, debilitating illness, and enormous economic costs that a
pandemic could wreak on the United States and the world. If I can leave
you with three messages from my testimony today, they are the
following. First, there is a consensus by leading global health
authorities that Tamiflu ' is effective and an important
tool in pandemic preparedness and response. Second, other nations are
currently well ahead of the United States in Tamiflu '
stockpiling. Finally, there are important practical constraints on the
production of Tamiflu ' that make immediate U.S. contractual
commitments for future pandemic supplies a necessity.
We at Roche want to continue to work closely with this
Subcommittee, HHS, and governments around the world to assist in
ensuring our pandemic preparedness. On behalf of Roche, thank you for
highlighting the importance of this critical issue, and I will be
pleased to answer any questions you may have.
Mr. Ferguson. Thank you very much. Dr. Tripp.
STATEMENT OF RALPH A. TRIPP
Mr. Tripp. Mr. Chairman and members of the subcommittee, I
am here today to tell you about the emerging pandemic threat of
Avian Influenza and how scientists at the University of Georgia
in collaboration with Alnylam Pharmaceuticals in Cambridge,
Massachusetts are developing novel and proven therapeutics to
prevent Avian Influenza virus and other important respiratory
virus infections. My comments today echo those concerns of the
CDC, World Health Organization, and Institute of Medicine, and
others about the need for preparing for pandemic flu.
I am keenly aware of the threat that mankind faces by
influenza and other important respiratory viruses having worked
at the Center for Disease Control for 7 years in the
Respiratory and Enteric Viruses Branch before moving to the
University of Georgia to become the Georgia Research Alliance
Eminent Scholar in vaccine development, as well as the director
of the Center for Disease Intervention there. And I must
reemphasize the imminent threat of an influenza pandemic.
As we are all aware, pandemic flu spreads rapidly and
during the pandemics of 1957 and 1968, those viruses took less
than 3 to 4 months to go from the site of origin in Southeast
Asia to North America and Europe. Clearly, the conditions are
more favorable for spread these days with the air travel
possibilities so an outbreak could occur in a matter of days
around cities throughout the world. Once a pandemic flu
emerges, we probably won't be able to prevent the global
spread, but if we are prepared with things such as antivirals,
it can significantly reduce its impact.
The current outbreak of flu in Asia known as H5N1 is
thought to have significantly heightened the risk of another
flu pandemic as reported by the World Health Organization.
Since the emergence of H5N1 in poultry in mid-December 2003,
this strain has devastated the poultry industry in nine
different countries in Southeast Asia. Clearly, it would have a
similar impact if it came to the United States.
There has also been numerous reports of human infection by
this strain, as has been described by the witnesses today.
Scientists at the University in Georgia, in collaboration with
investigators at the Center for Disease Control and Alnylam
Pharmaceuticals, recognize that multiple approaches are going
to be necessary to protect the human population from the newly
emerging virus strains such as H5N1.
Vaccines are obviously the mainstay of prophylaxis against
influenza, but there are technical and safety issues that we
have all heard about that must be overcome. These include
difficulty in predicting which strains of virus may emerge,
difficulty in preparing sufficient quantities of the vaccine to
meet the global demand, and clearly in storage and distribution
of these vaccines.
Antivirals have been shown to be very effective in treating
common influenza. However, as you have heard, H5N1, Avian Flu
is resistant to two of the most common drugs, rimantadine and
amantadine and now they is some evidence and literature that
the virus may be developing resistance to a newly developed
drug Tamiflu or oseltamivir. The evidence for viral resistance
to antiviral drugs indicates that more than one drug is going
to be necessary to combat emerging flu and new, novel
approaches are going to be necessary to enhance effectiveness
of these drugs, as well as to prevent viral resistance to the
existing drugs.
In my laboratory at the University of Georgia we are
working with new, breakthrough technology with Alnylam
Pharmaceuticals called RNA interference. RNA interference is a
natural process. It occurs in all the cells of our body. The
process is meted by activity of short strands of RNA that
silence host genes and control development. We have been able
to harness that power to actually generally RNA-interfering
drugs that prevent respiratory virus infection, particularly
for respiratory syncytial virus. And now we have shown that
with these same RNA interference drugs are useful in preventing
infection by highly pathogenic H5N1 and H7 strains of flu.
We have also shown these RNA interference drugs are useful
both prophylactically and therapeutically to prevent
respiratory syncytial virus, and this is a virus that is the
leading cause of series lower respiratory tract illness in
infants and young children worldwide for which there is no
vaccine and treatments are limited.
So the studies from my laboratory at the University of
Georgia have shown the potential to create powerful
therapeutics that meet the demand for new drugs with higher
potency, lower toxicity, and having a much higher degree of
specificity in that they only attack the cells that are
affected by the virus.
So given the pending threat of influenza, it is absolutely
necessary that our disease intervention strategies move beyond
the standard vaccine and into a new class of proven
preventative and therapeutic treatments. With RNA interference,
the creation of a safer and more accurate antiviral is
certainly within reach and on the horizon. These specific
antiviral therapeutics can be developed rapidly, they can
produce the high levels, and they can be stockpiled or stored
as needed.
So I am here today to urge the Members of Congress to bring
universities like the University of Georgia together with
private sector companies like Alnylam Pharmaceuticals to
develop breakthrough solutions to address the important human
diseases like pandemic flu and provide alternatives to
antiviral drugs, certainly which some have become resistant to.
Support for this new and proven technology will provide an
unprecedented means to control pandemic flu, as well as address
other important viral infections. And clearly, without support
for this type of a robust research program, we are destined to
relive the pandemics of the past. And in developing these RNA-
interfering drugs, we are developing new tools to address any
emerging infectious virus. And I would like to thank you for
your time.
[The prepared statement of Ralph A. Tripp follows:]
Prepared Statement of Ralph A. Tripp, Director, Center for Disease
Intervention
SUMMARY
The World Health Organization (WHO) and influenza experts worldwide
warn that an influenza virus (flu) pandemic is inevitable and imminent
and will likely be caused by widespread distribution of an avian
influenza virus, e.g. avian flu.
Vaccines are the mainstay of prophylaxis against influenza, but
there is currently no vaccine capable of protecting humans from
infection with avian flu.Currently approved anti-viral drugs may be
useful to treat pandemic flu but their effectiveness is limited by
development of resistance.
Novel and new anti-viral approaches are required to enhance the
effectiveness of existing anti-viral drugs, prevent viral resistance to
existing drugs, and to provide a strategy to combat avian flu and other
important respiratory viral diseases.
The discovery of RNA interference, or RNAi has revolutionized our
ability to offer new, potent and specific viral disease intervention.
RNAi is a natural biological process that occurs in all of our cells.
The process is mediated by the activity of short strands of RNA that
specifically silence the targeted gene of interest.
We have harnessed the power of RNAi to silence respiratory virus
infection and disease by targeting viral genes. We have shown that RNAi
is very potent, specific, and reactive for all strains of virus
targeted.
RNAi is a new breakthrough solution to address pandemic flu that is
on the horizon. Support for this new and proven technology will provide
an unprecedented means to control pandemic flu and other important
respiratory virus infections that carry a high disease burden on
mankind.
Pandemic Influenza (flu):
A pandemic is an epidemic that spreads rapidly around the world
with high rates of illness and death. While people are exposed to
different strains of the flu virus many times in their lives, about
three or four times every century a radically different strain of flu
causes a pandemic.
Such warnings by the World Health Organization, Centers for Disease
Control, National Institutes of Health and Institute of Medice have
been fueled by the persistence of a highly virulent strain of avian
influenza virus in Asia that experts fear could trigger another
influenza pandemic.
Influenza pandemics are not new. In the 20th century, mankind has
faced three influenza pandemics. The first was the devastating 1918
``Spanish Flu'' pandemic, as well as two less severe influenza
pandemics in 1957 and 1968.
Key facts of pandemic flu:
Pandemic flu occurs every few decades and spreads rapidly to affect
most countries and regions around the world. Unlike the ``ordinary''
flu that usually occurs every winter, pandemic flu can occur at any
time of year
Pandemic flu is much more serious than ``ordinary'' flu--as much as
a quarter of the population may be affected--maybe more.
A serious pandemic is also likely to cause many deaths, disrupt the
daily life of many people and cause intense pressure on health, poultry
and other industries.
What is pandemic flu caused by?
The emergence of a new flu virus which is markedly different from
recently circulating strains and to which few people have any immunity.
Strategies to protect against pandemic flu:
Vaccines are the mainstay of prophylaxis against influenza, but
there are technical and safety issues that must be overcome, and
problems in producing sufficient vaccine to meet global requirements.
There is no vaccine ready to protect against pandemic flu.
Currently approved anti-viral drugs can be used to treat pandemic
flu but their effectiveness is limited by development of drug
resistance.
The nature of the next pandemic flu: Avian Influenza:
WHO and influenza experts worldwide are concerned that the recent
appearance and widespread distribution of an avian influenza virus,
influenza A/H5N1 (H5N1) ``has the potential to ignite the next
pandemic'', World Health Organization, December 2004.
What is Avian Influenza?
Avian influenza is a contagious disease of birds and poultry caused
by influenza A viruses. All bird species are susceptible to infection,
but domestic poultry flocks are especially vulnerable. Infection can
cause epidemics associated with severe illness, high death rates, and
economic devastation.
Where does Avian Influenza occur?
Avian flu occurs worldwide. The current outbreak of highly
pathogenic avian flu (H5N1) began in Asia and has to date affected
poultry in nine countries in Asia. In three of these countries, H5N1
strain has also infected people.
How does Avian Influenza spread?
Avian flu is spread in poultry flocks either via respiratory
secretions or contact with contaminated droppings. People are usually
infected through close contact with infected birds or their feces.
Person-to-person spread, so far appears to difficult.
Protecting the human population from Avian Influenza:
There is currently no vaccine capable of protecting humans from
infection, and effectiveness of existing anti-virals is not well
understood.
Why I am here today:
I am here today to tell you about the emerging pandemic threat from
avian influenza virus and how scientists at the University of Georgia
are developing novel therapeutics with Alnylam Pharmaceuticals,
Cambridge, MA to treat and prevent avian influenza and other important
respiratory viral infections.
My concerns echo those of the Centers for Disease Control, National
Institutes of Health, the World Health Organization, and Institute of
Medicine which all warn of the need for pandemic flu preparedness,
particularly for avian influenza.
What is the potential impact of Avian Influenza?
The emergence of new influenza A virus subtypes have caused all
three known flu pandemics, all of which spread around the world within
1 year of being detected.
1918-19, ``Spanish flu'', [H1N1]: caused the highest number of
known influenza deaths: more than 500,000 people died in the United
States, and up to 50 million people may have died worldwide. Nearly
half of those who died were young, healthy adults. Influenza A (H1N1)
viruses still circulate today after being introduced again into the
human population in the 1970s.
1957-58, ``Asian flu,'' [H2N2], caused about 70,000 deaths in the
United States. First identified in China in late February 1957, the
Asian flu spread to the United States by June 1957.
1968-69, ``Hong Kong flu,'' [H3N2), caused about 34,000 deaths in
the United States. This virus was first detected in Hong Kong in early
1968 and spread to the United States later that year. Influenza A
(H3N2) viruses still circulate today.
Historical patterns and influenza:
Influenza pandemics can be expected to occur, on average, three to
four times each century when new virus subtypes emerge and are readily
transmitted from person-to-person.
Pandemic flu spreads rapidly. During the pandemics of 1957 and
1968, the viruses took only 3-4 months to spread from southeast Asia--
where they were first identified--to Europe and North America.
Today, conditions are far more favorable to the spread flu. With
high population density, and ease of air travel around the world, an
outbreak could spread to virtually every city in the world in a matter
of a few days.
Influenza virus disease intervention strategies:
Multiple approaches will be required to protect the human
population from newly emerging influenza virus strains such as H5N1 and
others.
Vaccines are the mainstay of prophylaxis against influenza, but
there are technical and safety issues that must be overcome.
Anti-viral agents have been shown to be effective toward treating
influenza subtypes; however, avian flu (H5N1) is resistant to two
common influenza drugs, rimantadine and amantadine, but newly developed
drugs such as Tamiflu and Relenza appear to be somewhat effective.
The evidence for viral resistance to anti-viral agents indicates
that more than one drug will be necessary to combat influenza.
Novel new anti-viral approaches--RNA Interference (RNAi):
New anti-viral drugs are required to enhance the effectiveness of
current drugs and prevent drug resistance.
In my laboratory at the University of Georgia, we are working with
new breakthrough technology called RNA interference, or RNAi. RNAi is a
natural biological process that occurs in all of our cells to control
development. RNAi is mediated by the activity of short strands of RNA
that specifically silence the targeted gene of interest.
We have harnessed the power of RNAi to silence respiratory virus
infection and disease by targeting viral genes. We have shown that RNAi
is very potent, specific, and reactive for all strains of virus
targeted. We have shown that RNAi prophylaxis and therapeutic treatment
can be used to effectively silence respiratory syncytial virus (RSV)
which is the leading cause of serious lower respiratory tract in
infants and young children worldwide.
RNAi has the potential to create powerful therapeutics that meet
the demand for new drugs with higher potency, lower toxicity, and have
a high degree of specificity, i.e. only attack their target and do so
very efficiently.
RNAi and the pending threat of pandemic flu:
It is absolutely necessary that our disease intervention strategies
move beyond the standard vaccine and into a new class of proven
preventative and therapeutic treatments. With RNAi, the creation of a
safer, more accurate and efficient anti-viral treatment for pandemic
influenza is closer in reach.
Specific anti-viral RNAi therapeutics can be developed rapidly,
i.e. within several months, produced at high levels, and stock piled or
stored as needed.
RNAi is a new breakthrough solution to address pandemic flu that is
on the horizon. Support for this new and proven technology will provide
an unprecedented means to control pandemic flu and other important
respiratory virus infections that carry a high disease burden on
mankind.
Clearly, without support for this robust research program that can
prevent respiratory virus disease burden, and silence virus replication
and spread, we are doomed to relive the pandemics of the past. In
developing the RNAi disease intervention strategies, we are developing
tools to respond to any novel virus that may emerge.
Mr. Ferguson. Thank you very much to all of you, and with
that we will begin some questioning. The Chair recognizes
himself for the purpose of some questions.
Dr. Iacuzio, Dr. Gerberding in the testimony in the first
panel talked about Tamiflu when I was asking her questions
about antivirals, which seemed to be at odds with some
testimony that she had given last November. And I know that,
Dr. Pavia, you said you had some disagreements with some things
that Dr. Gerberding said earlier today. Specifically about the
effectiveness of Tamiflu with some strains of the Avian Flu,
Dr. Tripp just referenced that as well. How does what Dr.
Gerberding was saying square with your knowledge--I mean, you
make it--how does that square with your understanding of the
effectiveness of Tamiflu with regard to various strains of the
Avian Flu?
Mr. Iacuzio. There is scientifically published literature
that oseltamivir, Tamiflu, has been tested in the lab against
all known subtypes of Type A influenza, including all Avian
strains, N1 through the N9, which basically--you know, they
cover all the Type A viruses, and it is effective against all
those in the laboratory.
In addition, we have talked with officials, Klaus Stohr at
the World Health Organization about the latest data that he is
aware of from the Asian outbreak of Avian Flu out there, and
according to the notes that I have is that no deaths from any
individuals who have taken Tamiflu within the first 48 hours
have been reported to his knowledge. So this is what the WHO is
aware of as of this point in time.
Mr. Ferguson. I just want to make sure that there isn't
some new data, new information since last November when Dr.
Gerberding testified in front of Congress. She said she
believed Tamiflu was highly effective for strains that were
known. Is there anything new in the last several months that
would challenge that notion?
Mr. Iacuzio. No, there really isn't. There had been reports
of increased resistance reported in one paper in Japan, but the
data was from a study where children are one, underdosed; two,
they are not given the dose at the long enough duration; and
three, the isolates were isolated through a highly
sophisticated laboratory technology, which we don't know what
that means. I mean they were basically laboratory curiosities.
We don't believe that these are infectious strains.
Mr. Ferguson. So given that the data that you have and
published studies that you cited----
Mr. Iacuzio. Right.
Mr. Ferguson. [continuing] there seems to be a consensus
that Tamiflu is effective for Avian Flu, yet we have heard from
GAO and others that it seems to be inadequate, I guess, to put
it mildly. Our efforts to stockpile antivirals to prepare for
this--what everyone seems to think is an eventuality--seems to
be not the most aggressive course of action that we could be
taking. You have been in discussions--Roche has been in
discussions with the U.S. Government for 2 years or so to
negotiate the production of more Tamiflu for stockpiling
purposes. Obviously, negotiations that take 2 years or more,
every day that is lost is precious time when additional
antivirals could be being produced and stockpiled. Given that,
we are where we are.
If an order were placed tomorrow--we have heard World
Health Organization and others have recommended 25 to 50
percent of the population should have the ability to be
covered. You mentioned a number of countries which have already
placed orders or have begun stockpiling orders to cover 20 to
40 percent of their population. If the United States placed an
order for Tamiflu tomorrow to cover 25 percent of our
population, perhaps on the conservative side of what many of
these other countries are doing, what would be the timeline for
production? How would that affect your production capacity?
What would be the timeline for your ability to produce that?
And is there any way, if that is not real fast, that you would
be able to make investments or to be able to streamline that or
advance that timeline any quicker?
Mr. Iacuzio. Since we began the conversations with public
health officials in 2003, Roche globally has increased
production capability eight-fold. Since locally we were--a year
ago, February 2004 we were requested for considering a U.S.
production facility. Roche has, as I said in my statement, has
taken that initiative and that production facility we expect to
up and running by the third quarter of 2005, this year. With
that increased capacity both globally and the U.S. we would be
able to produce--because of existing orders that already have
been booked--about three million doses this fiscal year, by the
end of this year; 13 million doses that are remaining for 2006;
and by the end of 2007, another additional 70 million doses. So
by the end of 2007 we should be able to provide approximately
enough for 25 percent of the U.S. population.
Mr. Ferguson. That is your capacity? That is what you would
be able to do?
Mr. Iacuzio. If orders came in now because every day that
goes by additional countries are placing orders----
Mr. Ferguson. What has been ordered--what has the United
States ordered thus far?
Mr. Iacuzio. Right now we have firm commitment--well, the
U.S. has purchased 2.3 million doses, and there is a non-
binding letter of agreement for an additional, I believe, three
million doses.
Mr. Ferguson. So we are talking about less than six million
doses----
Mr. Iacuzio. Right.
Mr. Ferguson. [continuing] that the U.S. would be
stockpiling?
Mr. Iacuzio. At this point in time.
Mr. Ferguson. Is that enough?
Mr. Iacuzio. I think that is a question really for public
health officials.
Mr. Ferguson. Dr. Pavia, is that enough?
Mr. Pavia. It is clearly not enough. I think to find the
right number using good epidemiologic techniques is something
we haven't done yet----
Mr. Ferguson. Yes, but we can all agree that----
Mr. Pavia. [continuing] but the current amount----
Mr. Ferguson. [continuing] this is imperfect--estimating
what we would need is an imperfect science, but I think
something that we could probably all agree on is that six
million doses doesn't come close to being able to prepare us
for what we all agree is the eventuality of this catastrophe.
Mr. Pavia. It is a painfully small amount to have to use.
Mr. Ferguson. I am over my time. Mr. Allen.
Mr. Allen. Thank you. Thank you, Mr. Chairman. And I want
to thank all members of the panel.
Mr. Hosbach, I wanted to ask you about what incentives
industry needs to increase production capacity in the U.S. but
I think you pretty much answered that. I mean you said increase
vaccination rates for annual flus, get a public and private
distribution system in place, do vaccine liability protection,
and four, CDC would have to build the capacity to increase
stockpiles. Is there anything you would add to those four? Is
there anything you want to elaborate on that? Because, you
know, how do we get--obviously there is not enough
manufacturing capacity out there, and you are in Pennsylvania
and we thank you for that. But I wondered if there is anything
other than those four points that you would like to make on
this?
Mr. Hosbach. Well, I would really probably like to
emphasize the need to get every American to understand the
importance of influenza vaccine, being vaccinated. Increasing
those inter-pandemic immunization rates will continue to
encourage us to expand, as I had mentioned, others to enter the
marketplace, and I think you are already seeing some interest
from other players. But I think that it is important for
several reasons: one, not only for our expansion but that
people get used to being immunized; they know who to go to to
get immunized, that this becomes a routine and part of their
every effort to protect themselves against flu. I think that
will help us prepare in the long run for a pandemic.
Mr. Allen. Second question, can you talk about how the
regulatory process regarding vaccine development and production
differs between the U.S. and the E.U.? And part of that
question is whether or not more could be done to harmonize the
approval processes in the two continents--countries----
Mr. Hosbach. I am not truly a regulatory expert, and I
don't know the specific differences between the E.U. and the
U.S., but I do know that there are efforts to harmonize, that
much of what they do is similar, and I do know that there is a
continuous dialog between the FDA and European Union officials.
Mr. Allen. Just one more question for you. Could you
elaborate a little bit on the SEC issue? Dr. Gerberding
referred to it. I think you mentioned it in your testimony. We
are up here trying to figure out what that is all about.
Mr. Hosbach. Well, you know, it comes from a staff
accounting bulletin, which our accounting firms and several
accounting firms have interpreted in one way wouldn't allow us
to participate or recognize the revenue from the stockpile, so
that becomes an issue for us because we would like to have our
revenue match our activity.
Mr. Allen. So you would only recognize the revenue from the
vaccine when the vaccines were used? Is that the----
Mr. Hosbach. That is correct. And I think this all stems
from some of the issues in other larger industries that have
had some accounting problems. And so I think that this is a
very conservative interpretation, and certainly we need some
assistance in clarifying that or perhaps even modifying
contracts with CDC that might be able to get around the issue.
Mr. Allen. Okay. Thank you. Dr. Crosse, you testified that
insufficient hospital and health workforce capacity is an area
of concern. Could you give us your characterization of the
adequacy of our hospital and health workforce capacity to deal
with the next pandemic? And if you can and you think there are
gaps--I am sure there are gaps--could you point to specific
provisions in the fiscal 2006 budget that are aimed at
addressing those gaps?
Ms. Crosse. I can't give you numbers, but certainly
healthcare workforce shortages is a persisting problem. One
concern that is especially problematic in a pandemic is that
the healthcare workforce would be a highly exposed population
and they might themselves become ill or have family members who
were ill that they would need to care for. So you might
exacerbate any shortages. In this past winter's vaccine
shortages, healthcare workforce was not among the priority
groups for vaccination, so that would need to be an issue that
was considered if you had widespread outbreaks.
There are constant shortages in areas of the country of the
nursing workforce. When we did earlier work on bioterrorism
preparedness, we found that many communities were planning on
surge capacity by calling on their temporary nurse network, but
multiple hospitals were counting on the same nurses. And so I
think that the bioterrorism funding that has gone to increase
hospital planning and preparedness for bioterrorism is helping
them to work through some of that planning and to sort through
some of the issues. It still doesn't get the bodies there. And
the mobile hospitals that were mentioned that could be brought
in to be deployed, if you are having nationwide outbreaks, they
are still going to have to be staffed locally in all likelihood
so that some of the emergency medical care that might be
available to be flown in if there was an outbreak in one area
would not be available if you had a nationwide pandemic. And so
this is a continuing problem.
I can't point to the specific provisions. That would be
probably better addressed to the department, but there has been
funding through HRSA for hospital preparedness under the
bioterrorism funding programs.
Mr. Allen. Thank you. The only comment I would add is--this
is just an anecdote. I don't mean it as a matter of policy. My
son-in-law wants to go to nursing school; he has taken all the
prerequisites. He can't get into nursing school until the fall
of 2006 in Maine, and it has something to do with the number of
slots available. Anyway, thank you all for your testimony. And,
Mr. Chairman, I yield back.
Mr. Ferguson. Mr. Allen, we would be delighted to have your
son-in-law in New Jersey if he would like to come to nursing
school. Mr. Brown.
Mr. Brown. I already asked him if he would want to come to
New Jersey, and he said he wanted to come to Ohio instead.
Dr. Crosse, I want to follow Mr. Allen's question for a
moment and then a question for you, Dr. Iacuzio. Does the
bioterrorism funding in some sense, the increase in funding,
mask or--maybe mask is a good work--funding for other
preparedness for a pandemic outbreak or general public health
needs and infrastructure?
Ms. Crosse. I am not sure what you mean by mask. Is it
filling a broader set of needs or do you mean that it----
Mr. Brown. Or is it looking like it is filling a broader
set of needs but in some sense taking away from other public
health needs that we have seen?
Ms. Crosse. I don't think that we have done work recently
enough to be able to say how that has played out in the local
communities. There are some concerns, I think, that this money
coming in may be supplanting some of the funding that otherwise
might be provided. But I think it has been providing a broader
set of public health preparedness functions than would exist
without that funding. It has funded communication systems that
are not just used for bioterrorism but for all disease
reporting. It has provided some kinds of systems and
infrastructure that otherwise might not be in place. I can't
speak really to what it has done in terms of whether it has
supplanted other funding.
Mr. Brown. My concern is while CDC funding particularly has
not seen major increases in the last few years, unlike NIH
which deserved it also, and when there were increases I am not
sure that while we did do the right thing certainly for
bioterrorism preparedness and answering those issues and
preparing local communities, public health officials that we
didn't take away from the sort of the workaday infrastructure
building and whether it is an issue to like health disparities
or whether it is lead poisoning or whether it is nutrition
education or whether it is a whole host of issues. But that is
more a comment than a question.
Dr. Iacuzio, if I could, according to CDC flu viruses can
become resistant to antiviral treatments like Tamiflu. I have
done a lot of work on particularly international tuberculosis
issues and seen what MDR-TB has done in New York City was our
first really horrible experience I think a dozen plus years
ago. But we have seen what has happened if we don't follow the
DOTS treatment, if patients don't follow the DOTS treatments
pretty regularly and pretty precisely, and we know how
expensive it is and we know the cure rate, particularly in the
most common places for TB, but how the cure rate is pretty
difficult and not satisfying when drug resistance occurs. But
sticking more to Tamiflu, could you elaborate on the potential
and describe how, especially in a pandemic situation, public
health officials can best avoid the onset of drug resistance?
Mr. Iacuzio. I believe that the information that we have to
date indicates that Tamiflu is safe and effective and there is
a low level of resistance. And that has been in published
studies. I guess the only thing that I would add is that the
data that we do see from places like Japan where they are
dosing at a lower dose than has been recommended through the
rest of the world and for a shorter duration of time, that
probably is the scenario for generating resistance. And there
have been a couple of papers that have been published in Japan
about increased resistance to antiviral drugs. And it is the
same with antibiotics; if you are going to treat, you need to
treat with enough antibiotic drug and you need to treat long
enough. And if you do the opposite, then you are creating a
scenario to generate resistance. I guess that is what I am
trying to say. So you need enough drugs in consistent dosing.
Mr. Brown. Well, I guess this is fairly evident, but you
need enough drugs, you need a distribution mechanism to reach
remote areas, but to reach them with a large enough supply and
with an even-handed distribution and a consistent patient/nurse
or patient--whatever the healthcare provider is--relationship
that will mean full compliance.
Mr. Iacuzio. Right. And that is why I believe that, you
know, discussions of just stockpiling need to go beyond just a
big stockpile but actually the whole distribution of how that
drug gets out to the individuals who need it.
Mr. Brown. This is a bit off, but are people with less
education typically less likely to be compliant people in a
developing world who are not just more remote in terms of
distance but less familiar with the healthcare system, all of
that? Those would be people likely less compliant----
Mr. Iacuzio. That is----
Mr. Brown. [continuing] or do we know that?
Mr. Iacuzio. That is a good question that I really--I am
not prepared to answer that----
Mr. Brown. Okay.
Mr. Iacuzio. [continuing] personally.
Mr. Brown. Okay. Fair enough. All right. Thanks.
Mr. Ferguson. We are going to do another round of questions
if that is all right. I don't think it should take too long.
The Chair recognizes himself.
Dr. Hosbach, can you go through the steps and the timeline
that it takes for a company from the decision to start, say, an
Avian Flu vaccine and actually finishing production in as much
detail as you would like? Can you just walk us through from the
decision to do that to when it actually is produced and how
much time that takes as well?
Mr. Hosbach. Well, overall, as you heard I think earlier,
the process itself will take about 6 months from start to
getting doses produced and started to get out the door. The
initial steps really are a collaboration with governments and
other agencies in terms of identifying that strain, as you
indicated, but then getting the reassortant strain that will
grow in eggs and start practicing that in our laboratories and
also handling it within our manufacturing facility to a point
at which it becomes adapted to eggs. From that point on we
start producing the vaccine within the egg itself and then
activate the virus and harvest the virus from the eggs. I think
you will find it interesting that actually the manufacturing
piece of it is the smallest portion of the entire chain of
production and release. There are large number of release
tests, quality standards that need to be met. And actually the
release testing those points of quality to observe really take
the longest part of the production process. So it is not the
actual making it in the eggs that takes long; it is the steps
that you have to go through to ensure that you are making a
safe and quality and effective product.
Mr. Ferguson. Where do liability concerns fit into that
process? I mean you mentioned a coordinated effort with
government at the very beginning. How do liability concerns fit
into that process and how do they affect the timeline of being
able to produce the product?
Mr. Hosbach. I think, you know, liability concerns enter
in, especially when we are about to enter into something like
clinical trials. That is critically important because you are
now starting to introduce this into society and introduce this
into human subjects. So that becomes one facet of liability
that is of concern. But, of course, then once you are ready to
release product into the general population, then it is a huge
concern because you are not just immunizing perhaps 85 million
people; you are immunizing 300 million people.
And I think that if you go back to the mid-'70's, Congress
then thought it was important enough in that environment to
provide indemnification to companies and to physicians, et
cetera. And I think within the current environment that would
especially be appropriate. It would put companies in great
peril given the unknowns about the actual properties of a new
pandemic strain that is a total shift from things that we have
utilized before. And given the fact that we only have so few
manufacturers, I think you would be putting major assets in
harm's way; and not just assets of these pharmaceutical
companies, but assets to public health.
Mr. Ferguson. I am told that, as you referenced in the
1970's with the Swine Flu, that indemnification was a major
component to being able to produce a product that was
necessary. And as you are leading to, would indemnification
hasten that process at all? Would it shorten the timeline to be
able to get these products to market?
Mr. Hosbach. Yes, I think----
Mr. Ferguson. And we are looking at a----
Mr. Hosbach. [continuing] in the end-stages it would----
Mr. Ferguson. And we are looking at a serious problem.
Mr. Hosbach. In terms of filling and packaging and having
the material ready to release, I think that end part of the
process could be expedited.
Mr. Ferguson. Okay. Mr. Brown, did you have any other
questions?
Mr. Brown. A fairly general question, but one that I have
not really been satisfied with the answers in the past just
because I don't understand it particularly well. We all read
about problems with antibiotic resistance. We read about, you
know, the way that animals that ranchers and farmers and
perhaps veterinarians treat animals prophylactically, partly
for growth hormones with antibiotics, partly to protect them
prophylactically as the chickens or the cattle are put in small
areas. We read about problems obviously with other kinds of
antibiotic resistance, physicians over-prescribing, patients
demanding when they have a virus they want an antibiotic. I
wanted to ask the private sector people here but really any of
you to comment. What can Government do to encourage better
research and production, getting in the pipeline of antibiotics
and antivirals and anti-retrovirals and anti-parasitics?
Mr. Pavia. Well, I will take that on since, as you know,
IDSA has been very involved with that. I think that there are
several components to it. One is the limitation of
inappropriate use in animal husbandry. And that has come up
over and over again. FDA has come up with a process for
reviewing that. There is a possibility that antivirals could be
used to protect chicken flocks with potential disastrous
effects on antiviral resistance if the supplies existed.
The other is education. And there have been efforts to
educate patients that have been moderately successful.
Educating physicians is another aspect of that. But I think the
biggest problem is that we need more agents. Whatever we do to
prevent the emergence of resistance or to slow it, it is
inevitable. It is the nature of the organisms that they mutate
faster than we can develop new drugs. And so we need new agents
and we need to continue to do the things that are necessary to
have a full pipeline. And to do that we have to understand the
profit motives and what it takes to keep a full pipeline.
Mr. Tripp. I would agree with that. One of our goals is
obviously to develop these new breakthrough technologies with
Alnylam Pharmaceuticals on RNA interference. These drugs target
the actual structural components of the viruses that are very
conservative amongst all strains. We have shown these drugs are
very effective at targeting and preventing infection of all
strains of RSV, for example. And now we are looking at the H5
and H7 strains of influenza. You know, having another tool in
your tool belt is the key to preventing resistance. And, of
course, following protocol is also important. But I would
really recommend that there is more of a linkage in bring
private sector companies to the table with current research
efforts at universities such as I spoke about today.
Ms. Crosse. I would just add that we examined this issue of
antibiotic resistance from the use of antibiotics in animal
feed last year and issued a report with recommendations to FDA
to step up its process of review and action on some of the
antibiotics of concern. They have taken many years, and we have
urged that they speed their process to try to slow down some of
these problems from occurring where there is good evidence that
resistance is arising from the use among animal flocks. There
are other countries who have controls in place and have seen
decreases in the prevalence of antibiotic resistance strains
among their human population.
Mr. Ferguson. Just as we close I just want to thank all of
our panelists for being here today. There certainly seems to be
a consensus that there are serious problems down the road, and
we take your exaltations and your advice very seriously and we
hope to be taking actions as well. Thank you very much.
[Whereupon, at 1:13 p.m., the subcommittee was adjourned.]