[House Hearing, 109 Congress]
[From the U.S. Government Publishing Office]
THE STATE OF READINESS FOR THE 2005-2006 FLU SEASON
=======================================================================
HEARING
before the
SUBCOMMITTEE ON
OVERSIGHT AND INVESTIGATIONS
of the
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED NINTH CONGRESS
FIRST SESSION
__________
MAY 4, 2005
__________
Serial No. 109-79
__________
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 Oversight and Investigations
ED WHITFIELD, Kentucky, Chairman
CLIFF STEARNS, Florida BART STUPAK, Michigan
CHARLES W. ``CHIP'' PICKERING, Ranking Member
Mississippi DIANA DeGETTE, Colorado
CHARLES F. BASS, New Hampshire JAN SCHAKOWSKY, Illinois
GREG WALDEN, Oregon JAY INSLEE, Washington
MIKE FERGUSON, New Jersey TAMMY BALDWIN, Wisconsin
MICHAEL C. BURGESS, Texas HENRY A. WAXMAN, California
MARSHA BLACKBURN, Tennessee JOHN D. DINGELL, Michigan,
JOE BARTON, Texas, (Ex Officio)
(Ex Officio)
(ii)
C O N T E N T S
__________
Page
Testimony of:
Gellin, Bruce G., Director, National Vaccine Program,
Department of Health and Human Services.................... 14
Gerberding, Julie Louise, Director, Centers for Disease
Control and Prevention..................................... 10
Goodman, Jesse L., Director, Center for Biologics Evaluation
and Research, Food and Drug Administration................. 20
(iii)
THE STATE OF READINESS FOR THE 2005-2006 FLU SEASON
----------
WEDNESDAY, MAY 4, 2005
House of Representatives,
Committee on Energy and Commerce,
Subcommittee on Oversight and Investigations,
Washington, DC.
The subcommittee met, pursuant to notice, at 2:21 p.m., in
room 2123, Rayburn House Office Building, Hon. Ed Whitfield
(chairman) presiding.
Members present: Representatives Whitfield, Stearns,
Ferguson, Burgess, Blackburn, Barton (ex officio), Stupak,
DeGette, Schakowsky, Inslee, and Baldwin.
Staff present: Anthony Cooke, majority counsel; Alan
Slobodin, majority counsel; Mark Paoletta, chief counsel;
Clayton Matheson, research assistant; Chad Grant, clerk; Edith
Holleman, minority counsel; Voncille Hines, minority research
assistant; and Chris Knauer, minority investigator.
Mr. Whitfield. I would like to bring this hearing to order,
and I would like to apologize in advance to the witnesses that
we were a little late. We had a vote on the floor. But we are
excited about your being here today. We look forward to your
testimony on the state of readiness for the 2005-2006 flu
season.
At this time, as chairman, I will do my opening statement,
and we will go through the subcommittee, and then we will get
right to your testimony.
On October 5 of last year, one of our Nation's two largest
suppliers of influenza vaccine informed the American public
that it would be unable to provide any of the 46 to 48 million
doses it had planned. Overnight, the expected supply of flu
vaccine in the U.S. was cut nearly in half. Almost immediately
there were news reports of imminent delays and shortages that
could deprive millions of Americans who needed and wanted flu
shots from getting them. Elderly people, parents of young
children, adults with chronic illnesses, and countless other
Americans panicked and flocked to local doctors' offices,
healthcare clinics, and pharmacies to obtain the vaccine before
it ran out. Fortunately, the flu season proved to be a
relatively mild one, and coordination among HHS, the remaining
manufacturers and the public turned the concern of a national
shortage into a matter of some local and regional surpluses.
In light of last year, this committee must carefully
monitor preparations for the 2005-2006 flu season.
First, we need to look closely at the goals and strategies
behind our preparations for this season. We need a realistic
assessment of the manufacturers' capabilities and the vaccine
doses they should produce, and we must then plan accordingly.
Specifically, we must ensure FDA's focus on efforts to confirm
the entry, or reentry, of all available manufacturers into the
vaccine market; and we must be certain the U.S. is prepared for
all contingencies in which one or more of the producers of flu
vaccine fail to achieve the necessary license or suffer from
sterility or quality control problems that prevent distribution
of their vaccine.
Second, we must take advantage of this opportunity to
consider the manner in which we communicate important flu and
vaccination information to the public. This past year, the
American people listened to the media's troubling portrayals of
the shortage, and they panicked. Everywhere in the U.S.,
including my home district as well as others throughout the
country, worried people rushed to their doctors, rushed to
their pharmacists, where they all too often were either forced
to linger in long lines or were even turned away. It is
essential that our Nation's vaccine policymakers persistently
endeavor to communicate clearly and concisely accurate and up-
to-date information to the American people so that flu seasons
are never characterized by unnecessary concern or confusion.
I welcome today's witnesses and look forward to their
testimony. I hope this hearing will leave all of us with a more
complete understanding of what to expect for the 2005-2006 flu
season and more confidence in how our Nation's public health
stakeholders will manage the flu manufacture and vaccination
process.
With that, at this time I would like to welcome and
introduce Mr. Bart Stupak, the ranking minority member, for his
opening statement.
Mr. Stupak. Thank you, Mr. Chairman; and thank you for
holding this hearing.
Last year we had a very difficult flu season. In October,
just as most people were thinking about getting their flu
vaccine, the Centers for Disease Control was gearing up for
their vaccine education program, and the Nation learned that it
would only receive one-half of the 80 to 85 million doses of
flu vaccine that it was counting on. Because of sterility
problems in the manufacturing process, Chiron was not able to
produce any of the 46 million doses it had promised. If you
were not elderly, not very young, not disabled, or not with a
compromised immune system, you were asked to step aside and let
the more medically needy have their vaccine.
Americans did step aside, but the distribution to the
medically needy was haphazard. Some nursing homes, for example,
had trouble getting vaccine doses. Elderly persons lined up in
the morning at clinics only to find there were not enough doses
to go around. Health care providers struggled to make value
judgments about who in the high-risk populations, including
themselves, should get the limited number of vaccines. In
Michigan, for example, there were only 2 million doses of flu
vaccine available for 3.4 million high-risk individuals.
There are many questions about why the United States had so
few suppliers. By January, however, after one manufacturer
produced extra vaccine, there were available doses but not
enough customers. Approximately 3.5 million doses out of the 60
million were discarded.
We are now preparing for the next flu season. At this point
we have no more suppliers than we did a year ago. Sanofi is
planning to produce 50 to 60 million doses, and MedImmune will
produce another 3 million of the FluMist. Chiron hopes to
produce 25 to 30 million doses but has not yet been approved to
do so. Glaxo may enter the market with 10 million doses but has
not yet filed for a license. If all goes well, that would
provide 93 to 103 million doses, or 9 to 21 percent more doses
than this country has ever used. If these vaccine promises are
not fulfilled, we will have approximately the same amount that
we had last year or maybe even less.
Today I am interested in knowing what changes have been
made in the distribution and education system so that this year
the medically needy are served quickly and efficiently and
there is no waste of vaccine because populations have been
discouraged to receive their flu vaccine.
I also want to know why the drug companies are raising
their prices by 17 percent, citing market demand, and whether
this increased cost will discourage use.
In addition, I remain concerned that the Department of
Health and Human Services now seems to be relying on only one
domestic manufacturer to produce extra vaccine and to develop
new methods to manufacture flu vaccine. If anything goes wrong
with this domestic supplier, like it did at Chiron, America
will be in serious trouble.
There has been concern about our flu vaccine policy for
some time. Two years ago, several members of this committee
sent a letter asking for a hearing on our flu vaccine policy.
Flu kills 35,000 people per year even without a shortage. I
look forward to hearing from the witnesses today about their
agency's plan to ensure an adequate supply and appropriate
distribution of this life-saving vaccine.
In addition, Mr. Chairman, I am sorry drug companies are
not here to answer the questions about their intent and
interests in meeting this Nation's needs. To get a complete
picture of the situation, we need to hear directly from the
manufacturers of the flu vaccine, and I look forward to such a
hearing.
Thank you, Mr. Chairman. I yield back the balance of my
time.
Mr. Whitfield. Thank you very much.
We will be calling on opening statements in order of
appearance at the committee. So at this time I would like to
call on Mrs. Blackburn of Tennessee for her opening statement.
Mrs. Blackburn. Thank you, Mr. Chairman; and I want to
thank our guests who are with us today for taking the time to
be here. I will waive my statement and reserve the time for
questions.
Mr. Whitfield. Mrs. Blackburn waives her opening statement.
At this time, I recognize Ms. DeGette of Colorado.
Ms. DeGette. Thank you very much, Mr. Chairman, for holding
this hearing. I would ask unanimous consent to put my full
statement in the record.
Mr. Whitfield. Without objection.
Ms. DeGette. I commend the chairman for having the hearing.
I also think we need some follow-up hearings on an issue that
has been of great concern to me, and that is the avian flu,
which isn't really the topic for today, but I think it is the
kind of the elephant in the room, if you will, because--and I
see our witnesses nodding in agreement. So I hope we can do
that.
But, with respect to today's topic, I am concerned, like my
colleagues, about our system for flu vaccine production. We
have three manufacturers committed to supplying the U.S. with
flu vaccine, but there have been concerns for many years that
our system doesn't adequately support these manufacturers; and,
also, the danger exists that the yearly destruction of unused
flu vaccine creates a disincentive for innovation and adequate
supply.
Last year, Colorado, my State, was among the first States
hit by the flu strain known as Fujian A, which was not included
in the 2004 flu vaccine. This flu strain for unknown reasons
disproportionately affected children and caused at least 11
deaths last year. We need to do better, and I hope that the
witnesses today can improve our understanding of the public
health issues and also describe the technological advances in
virus identification and antiviral production, because, as we
all know, the flu vaccine for any given year may not actually
cover all the viruses that go around. And, finally, I would
like the witnesses to talk about how prepared the U.S. is for a
flu pandemic, not just avian flu but any flu.
In late 2002, the SARS virus disrupted travel and tourism
and claimed the lives of many people. Now, I know the World
Health Organization has established a global monitoring system
to track influenza outbreaks, but the cost of complying with
this system is certainly too much for the world's poorer
nations where some of these viruses originate. I hope the
witnesses will talk about the adequacy of the surveillance
system and also our Nation's ability to cope with the pandemic.
It is my understanding that countries like Japan, Finland,
and Australia are stockpiling antiviral treatments against
pandemic flu for about a quarter of their population. Our
stockpile in the U.S. is only about 1 percent of the
population. So I would hope that we can talk about that as well
as the other issues raised by the ranking member, the chairman,
and others.
With that, Mr. Chairman, I yield back the balance of my
time.
[The prepared statement of Hon. Diana DeGette follows:]
Prepared Statement of Hon. Diana DeGette, a Representative in Congress
from the State of Wyoming
Flu related spending by the Department of Health and Human Services
has risen almost sevenfold over the past 5 years. While for some
individuals a flu infection is merely a few days sick in bed, for other
more vulnerable populations, the flu can cause serious illness and even
death. Even with all the advances of 21st century medicine, 30,000
Americans die from flu or flu-related illnesses each year. In some
studies, vaccination against flu has shown to provide protection to
between 70 and 90 percent of healthy adults. Unfortunately, some of our
vulnerable populations, including health workers, have dismal rates of
vaccination. We must do better.
I commend the Chairman for holding this hearing and agree that we
need to examine this important issue now, before the next crisis. It is
my understanding that many of the flu vaccine manufacturing has begun
this month in preparation for next year's flu season. I hope that
today's hearing will provide insights that will improve our readiness.
Like many of my colleagues, I remain concerned about the United
States system for flu vaccine production. We have at least 3
manufacturers committed to supplying the U.S. with flu vaccine, but
there have been concerns for many years that our system does not
adequately support these manufacturers. Additionally, the danger exists
that the yearly destruction of unused flu vaccine creates a
disincentive for innovation and adequate supply.
Last year, Colorado was among the first states hit by the flu
strain known as Fujian A, which was not included in the 2004 flu
vaccine. This flu strain, for unknown reasons, disproportionately
affected children, and caused at least 11 deaths of children last year.
We clearly need to do better. I hope that the three witnesses here with
us today will improve our understanding of this public health issue and
describe the technological advances in virus identification and
antiviral production.
In addition to concerns about flu vaccine supply, I hope that our
three expert witnesses will also comment on how prepared the U.S. is
for a flu pandemic.
In late 2002, the SARS virus disrupted travel and tourism and
claimed the lives of many people. I know that the World Health
Organization has established a global monitoring system to track
influenza outbreaks, but the cost of complying with the system is
certainly too much for the world's poorer nations. I hope that the
witnesses will comment about the adequacy of this surveillance system
and our nation's ability to cope with an outbreak. It is my
understanding that countries such as Japan, Finland and Australia are
stockpiling antiviral treatments against pandemic flu for up to one
quarter of their nations' population. The U.S. stockpile is maintained
for only 1 percent of our population. We may need to reexamine this
strategy.
Many experts have stated that in addition to surveillance, we need
a reliable and flexible vaccine production system. Last year, the
license suspension of the Chiron company's vaccine manufacturing plant
in the U.K. was a wake up call to all of us. In addition to a
``shortage'' of supply, we also were faced with educating the public
about appropriate distribution and recipients. I hope that the
witnesses will help us understand what went wrong last year and what
lessons were learned.
This hearing continues this Committee's examination of FDA's
ability to protect the public's health. It is my understanding that
there may be inadequate funding for FDA inspectors to travel overseas
and scrutinize manufacturing facilities. I hope that Dr. Goodman from
FDA's Center for Biologics Evaluation and Research will describe these
current challenges. Drug safety has been of great interest to me and
this Committee for a number of years, and the situation at the Chiron
plant is only one example of our concerns being realized. We clearly
must take steps to ensure that history is not repeated.
Mr. Whitfield. Thank you very much.
At this time, I would recognize Dr. Burgess for his opening
statement.
Mr. Burgess. Mr. Chairman, thank you for calling this
important hearing on public health readiness and how it relates
to influenza outbreaks. You know, we have to work with our
public health agencies to ensure access to adequate supplies of
vaccines are present but at the same time work with the
manufacturers to make certain that they have the ability to
produce flu vaccine.
Some of the concerns I have regarding the vaccine
availability aren't with today's focus on the flu vaccine
supply. Many people have forgotten that since 2000 we have also
had shortages of vaccine that protect against eight childhood
diseases. The flu vaccine shortage was only symptomatic of the
broader vaccine supply problem: There are only a handful of
manufacturers making vaccines for Americans. Three
manufacturers had licensed products for flu vaccines last year,
many childhood vaccines have only one manufacturer, and none
have more than two manufacturers, increasing the risk of
shortages.
The question comes up as to why there are so few
manufacturers. Certainly the vaccine business is complex in its
development, complex in its manufacturing, and certainly
complex because of the regulatory challenges, many of which
Congress has imposed upon it. Obviously, that all adds to the
cost. Vaccines, however, are a fairly low-margin business, and
again that may be partly our responsibility as well because
there are some price controls on vaccines.
Then, finally, vaccines have one of the greatest liability
burdens of any medical product; and the statute of limitations,
particularly for childhood vaccines, is incredibly long. We
need to address the overall issue of vaccines supply in this
country, and I encourage the country to take up the broader
issue of ensuring a stable supply for all vaccines this year.
I yield back.
Mr. Whitfield. Thank you very much.
At this time, I recognize Ms. Schakowsky for her opening
statement.
Ms. Schakowsky. Thank you, Mr. Chairman.
Thirty thousand people die annually from the flu virus,
hundreds of thousands of others end up in the hospital, and no
American should again be asked to compromise their health
because of the failures of the Bush administration to provide
sufficient doses of the flu vaccine.
Last October, we learned that we would have only half the
expected supply of influenza vaccine for the fall and winter
flu season. When the Food and Drug Administration was told of
contamination at the Chiron facility, one the largest flu
vaccine producers, it failed to act in a meaningful way to
address the problem, which was secure additional vaccine
supplies elsewhere. We saw price gouges appear out of the
woodwork to profit from a public health crisis; and we saw many
who would normally seek a vaccination, those at greater risks
of contracting the flu, foregoing shots.
Had the FDA taken the appropriate course of action, last
year's vaccine shortage and perhaps unnecessary sickness and
loss of lives in the United States may have been avoided. None
of these problems occurred in other countries where the
government plays a far greater role in assuring affordable
access to health care. In fact, in Canada there was adequate
flu vaccine supply to sell to those Americans who were close
enough to the border to go across for a shot.
Last fall, Illinois Governor Rod Blagojevich, a leader in
the fight for affordable prescription drugs, including
prescription drug reimportation, acted to secure additional
vaccine supplies for the most vulnerable people in our State.
Although in a hearing we held last November the FDA indicated
to me that it planned to provide a decision within 2 or 3 weeks
of that time as to whether Illinois would be allowed to bring
vaccines into the country, Governor Blagojevich is still
awaiting FDA authorization.
So I want to know why, 5 months later, Illinois still has
not received a response from the FDA; and I want to know why,
given the fact that we are still entirely relying on foreign
sources to meet our flu vaccine needs, the Bush administration
is still adamantly blocking Illinois' reimportation efforts of
other life-saving medications. The FDA allowed politics to
trump personal health when it undermined Governor Blagojevich's
effort to address a serious health crisis. Why would a Federal
agency stall an emergency situation like the one we faced last
fall? The answer can only be because of their fear that
Governor Blagojevich's success in importing flu vaccine would
provide validation for his efforts to import prescription drugs
for the people of Illinois.
Today, the Wall Street Journal highlights how many doctors,
pharmacists, and hospitals across the U.S. already fear another
major shortage of flu shots. The Vice President of Amerinet,
Inc., a health care purchasing group of St. Louis, termed the
shortage in order of, ``a feeding frenzy.'' Manufacturers are
already charging at least 17 percent more for the flu shots,
reflecting this rush for advanced orders. According to the Wall
Street Journal, this, ``shows that the vaccine production
infrastructure remains nearly as fragile and outdated as it was
before last year's crisis.''
We should learn from mistakes made last year. I would like
to hear from the witnesses today what concrete actions the
administration is taking to ensure that this same fiasco will
not happen again. I want to hear what changes have been made to
our flu vaccine infrastructure since last year.
It is clear that we need better cooperation and information
sharing not only between the manufacturers and distributors but
also with the regulatory agencies of other countries where the
manufacturing plants are located. Because we are still clearly
relying on foreign sources to meet our flu vaccine needs, we
need to improve monitoring of and communication with those
sources. I would like to see how the FDA and CDC will work with
the State and local health officials, manufacturers, and the
public to improve distribution of available supply; and I want
to hear how it is that, after news of massive shortages, we
actually ended up with regional surpluses of the flu vaccine.
That fact is especially troubling because it means that many of
those who needed the vaccine but couldn't get it could have
avoided unnecessary illness.
At last year's hearing I questioned the Bush
administration's attitude toward vaccine accessibility. I was
disturbed by Vice President Cheney's explanation that vaccine
production just isn't profitable enough for private companies,
and I will ask the same question: Are the administration's
concerns for the high profits of the pharmaceutical companies
to take precedence over the health of the American people?
I want to be able to assure my constituents that there will
not be a shortage of flu vaccine in Illinois this fall, and I
hope this committee will be made aware in advance and in real
time of the status of flu vaccine production at the labs with
which we contract so that the 2005-2006 flu season will not be
a relapse of last year's problems.
Thank you, Mr. Chairman.
Mr. Whitfield. Thank you.
At this time, I will recognize the chairman of the Energy
and Commerce Committee, Mr. Barton of Texas, for his opening
statement.
Chairman Barton. Thank you, Mr. Chairman; and I am going to
submit my formal statement for the record.
I just want to briefly say I appreciate you holding this
hearing. I look forward to our panelists. We don't want to have
happen next year what happened this year. It was very
disconcerting to go from there was a big shortage and we were
rationing flu vaccinations to, later in the season, if you
wanted one, come in and get it. So we have a lot of issues.
But I guess the bottom line issue is going to be, are we
prepared for next year and will every American who wants a flu
vaccination next year be able to get one? I hope we get an
answer to that in the hearing today.
With that, Mr. Chairman, I would yield back.
[The prepared statement of Hon. Joe Barton follows:]
Prepared Statement of Hon. Joe Barton, Chairman, Committee on Energy
and Commerce
It's hardly seems like the flu season is past. But it is and it was
one of the most publicized ever. In just six months, it all starts
again. Millions of Americans will want a flu vaccination come this fall
and I think I can promise you that many are wondering right now whether
their vaccine will be available.
Last year, men and women in this country, many of them elderly,
stood in long December lines to get a flu vaccination when production
problems shut down the Chiron plant in Liverpool, England.
Almost immediately after the supply was interrupted, this Committee
held a hearing to try to determine what happened and how it could be
prevented in future seasons. Well, the future is upon us--vaccine
manufacture for the 2005-2006 flu season is well underway. We've
invited here today three representatives from the Department of Health
and Human Services to answer some simple questions: Are we ready? How
are we doing?
Let me be more specific. How many doses of flu vaccine do we expect
to need for the coming season and how many do we anticipate from the
companies manufacturing for the American market? When have we last
checked the progress of these manufacturers and what issues are
outstanding?
Looking back to the problems of last year, what are the specific
changes made to our flu vaccine policy and practice? Has FDA cleared up
its communication problems with the MHRA? What is the status of efforts
to introduce more vaccine manufacturers into the U.S. market? What
plans and contingencies do we have in place so we aren't caught flat-
footed in the event of another production failure like we experienced
last year?
Finally, while I recognize the complexities and uncertainties of
flu vaccine manufacture and distribution, I hope HHS can better
communicate to the American people the important information about
influenza and immunization. Last year, people heard warnings about
shortages then news of surplus. And each day more stories appear in the
press about the threats of deadly flu strains. People are worried about
the flu and whether their shots will be there in the fall. HHS must
keep them up to date with straightforward, clear, and measured
information.
I want to thank Mr. Whitfield for holding this important hearing.
And I look forward to today's testimony on the state of preparedness
for flu.
Mr. Whitfield. Thank you, Mr. Chairman.
At this time I would recognize Ms. Baldwin for her opening
statement.
Ms. Baldwin. Thank you, Mr. Chairman; and thank you to the
witnesses who are testifying before us today.
Like many of my colleagues, I was distressed by the series
of events last fall that led to the U.S. Having a severe
vaccine shortage. We ended up being pretty lucky, but we
certainly shouldn't have to be relying on luck to ensure the
health and well-being of Americans.
Preparing a flu vaccination strategy certainly seems to be
as much an art as it is a science. I understand the challenges
that we face in predicting which flu strains will be most
prevalent during the upcoming flu season and needing to prepare
the necessary vaccines months and months in advance, but I am
also interested in ways that we can strengthen this line of
defense for the health of Americans, either through changing
the actual vaccine production methods or changing the way that
we communicate and coordinate with other countries and vaccine
makers.
I am interested in hearing from our panel of experts today,
and specifically I am interested in knowing what are the
lessons learned from last year's experiences and how their
various agencies are moving forward to ensure that we have a
reliable flu vaccine supply. As Dr. Burgess mentioned in his
opening statement, I also share his interest in ensuring that
we have a reliable supply of other vital childhood
vaccinations. Thank you for being here today.
Mr. Chairman, thank you for holding this hearing, and I
look forward to our discussion.
Mr. Whitfield. Thank you.
At this time, I will recognize the gentleman from New
Jersey, Mr. Ferguson, for his opening statement.
Mr. Ferguson. Thank you, Mr. Chairman.
I appreciate our panelists for being here today. We thank
you very much.
We certainly have seen some major problems in the supply of
flu vaccine; and we certainly, as others have already said,
don't want a repeat of last year's problem. We know from
history that when we have seen severe flu problems literally
hundreds of thousands, millions of people can lose their lives.
Tens of thousands of people die in a typical flu season when
there is no vaccine problem, so certainly if there is a
shortage that exacerbates that problem. I am certainly
interested in the avian flu and some of the other issues that
have been described here, and I look forward to getting into
some of those issues when we have time for questioning.
I would only say it has been raised here in our opening
statements the topic of bringing in vaccines from Canada, and
perhaps that might be a model for bringing in drugs from Canada
or other countries on a broader scale. I would only suggest
that if we want to see similar problems that we have seen with
the flu vaccine, if we want to see similar problems in the
broader drug supply, let us start bringing in drugs from all
sorts of other countries.
Some have suggested, well, let us only bring in--why don't
we only import drugs from Canada and forget the health and
safety standards, the very high standards that we have here in
this country? Of course, that is a bit of a red herring. Canada
can't possibly make and manufacture and supply all the drugs
that they use and supply all the Americans who want to get
their drugs from Canada as well, whether it is the State of
Illinois or anybody else. Canada has simply become a post
office, not a manufacturer of drugs; and it has become common
knowledge that if you go across the border into Canada you are
not necessarily buying Canadian drugs, you are buying drugs
from South Africa or China or India or the Czech Republic or
any one of a host of other countries that don't have close to
the health and safety standards that we have in our country or
even that Canada has in their own country.
So I would suggest that if we want to cripple the companies
and the industry that are making these drugs, these life-saving
cures and medications in the first place, let us not use the
vaccine situation as the example of where we should go.
One of the problems, certainly one of the reasons we are
seeing such severe problems with the vaccine situation is
because we have driven manufacturers out of the business. We
have created an environment through our action in the Congress
and through other circumstances whereby companies just don't
find it sensible any longer to be in the business. If we want
to go that route for all medications, I would suggest, great,
let us just start importing drugs from other countries and not
worry about the health and safety standards, because that is
exactly where it is going to lead.
Thank you, Mr. Chairman. I yield back.
Mr. Whitfield. Thank you.
As you all are aware, this is an oversight investigation
subcommittee, and it is our custom to take testimony under
oath. And I would like to ask each of you--and before I ask
you, I do want to introduce all of you.
First of all, we have with us today Dr. Julie Gerberding,
who is the Director for the Centers for Disease Control and
Prevention; and we welcome you. In addition, we have Dr. Bruce
Gellin, who is the Director of the National Vaccine Program
Office at the Department of Health and Human Services; and then
we have Dr. Jesse Goodman, the Director of the Center for
Biologics, Evaluation and Research at the Food and Drug
Administration.
We do welcome all of you. We look forward to your
testimony, your expertise.
As I stated, we do take testimony under oath; and I would
ask you, do you have any objection to testifying under oath
this afternoon?
I would also advise you that, under the rules of the House
and the rules of the committee, you are entitled to be advised
by counsel at these hearings. Do you desire today to be advised
by counsel during your testimony?
Okay, in that case, if you would please rise and raise your
right hand, I would like to swear you in.
[Witnesses sworn.]
Mr. Whitfield. You are now under oath, and we look forward
to your testimony.
Dr. Gerberding, we will start with your testimony.
TESTIMONY OF JULIE LOUISE GERBERDING, DIRECTOR, CENTERS FOR
DISEASE CONTROL AND PREVENTION; BRUCE G. GELLIN, DIRECTOR,
NATIONAL VACCINE PROGRAM, DEPARTMENT OF HEALTH AND HUMAN
SERVICES; AND JESSE L. GOODMAN, DIRECTOR, CENTER FOR BIOLOGICS
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION
Ms. Gerberding. Thank you.
I thank the subcommittee for having this hearing. I think
this is a critical time for us to keep a strong focus on
influenza, and I appreciate your helping us do that from the
congressional perspective. I can assure you we are doing that
at the Department of Health and Human Services. Secretary
Leavitt is having the Department leaders meet every day on this
subject, so we are looking forward to giving you a perspective
on how we are preparing for the fall.
I wanted to start with a graphic that I think illustrates
one of the most important principles about influenza--on the
next graphic, please--and that is the fact that the virus
itself is so unbelievably unpredictable. This is kind of a time
line of influenza as it has evolved over the last century. Each
one of those arrows is the beginning of the appearance of a new
strain of flu, and each circle represents a pandemic that
started when a new strain appeared. So, in the last 100 years,
three times we have had major international pandemics as H1,
H2, and H3 appeared in the world and caused devastating
outbreaks. That is a very difficult event to predict.
Up in the right-hand corner of this graphic are the little
mini appearances of the avian isolates. And, of course, as you
mentioned, right now we are very concerned about avian
influenza in Asia, and we would look forward to being able to
update you on that topic.
But the point of all of this is that we don't know in any
given flu season whether this will be a pandemic year, a mild
season, when it will start, how long it will go, when it will
peak, how severe it will be, how many people will be affected,
will it be worse in adults or children. There is absolutely no
certainty about the strain or the characteristics of the flu
season on any given year, and that is a challenge for all of
us, even if we didn't have to face additional challenges.
But on my second graphic I have illustrated the outcome of
this past season. In the yellow bars here, the figures for the
coverage of the high-risk populations are presented. In the far
left graph is the comparison from this past year to the year
before and the number of young infants that were immunized. And
you can see that, despite our vaccine shortage, we were able to
achieve about a 50 percent immunization of that age group. This
is the first year that recommendation was made for those
children.
In the high-risk adults, those adults who have other
medical conditions, our immunization rates were not quite as
good as they were the year before. Among adults over 65, they
were very close to the year before but not quite the same.
Among health care workers, they were not quite the same. But,
overall, despite having 50 percent of the vaccine we predicted,
we came pretty close to achieving the immunization coverage
rates that we would have normally achieved in a year where we
had plenty of vaccine.
That is not a success, but it represents an effort of
hundreds and hundreds of people around the country as well as
the government and the private sector to really at a late date
make the doses that we did have available to as many of the
high-risk people as we can. And of course this illustrates that
it is not just the virus that is unpredictable, it is the
vaccine supply that is unpredictable, and it is the demand for
vaccine that is unpredictable as well.
So what are we doing about the vaccine supply? Well, the
first thing we are doing is buying lots of vaccine. Since 2004,
CDC's dollar investment in vaccines for flu has gone up by $118
million. In the President's proposed budget for fiscal year
2006, that would include $30 million for an insurance policy to
buy monovalent vaccine as a reserve if something goes awry with
one of the other manufacturers as well as the 20 million
purchase of vaccine for distribution to the States on top of
what is included in the Vaccines for Children program.
We are also providing a fair purchase price for this
vaccine. We think it is a good thing that over the last decade
the price paid for flu has gone from pennies to a price that
allows manufacturers to receive a fair reimbursement; and,
also, our government, through our Medicare and Medicaid
services, are reimbursing providers appropriately for providing
vaccine.
We are also planning scenarios. We will start the flu
season with a focus on high-risk people because we want the flu
shot in their arms first. Then, if the supply comes forward as
we are hopeful it will, we will be able to expand in to people
who have less risk from flu complications and ultimately into
healthy people as the season unfolds. But we will start the
season this way, with a clear message that that is the CDC's
priority. But people will have to understand, just as is true
in any year, the communication about flu does change as the
season progresses. We find out where it is peaking, we find out
if it is severe, we find out where vaccine supplies are short,
and we have to adjust our message as we go forward. We want
people to anticipate that and to expect that they will have to
pay attention, because the message will evolve.
I see there are many other steps and progress that I will
let my colleagues present to you, but, again, I just wanted to
say that we are very pleased that the committee is interested,
and we will do everything we can to keep you updated on all of
these unpredictabilities as we go forward and do as much as we
can to take the uncertainty out of the system. 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 Committee, I am pleased to be here
today to update you on the Centers for Disease Control and Prevention's
(CDC) efforts to address the influenza vaccine supply status and our
planning for the 2005-06 influenza season. We faced unprecedented
challenges during the 2004-2005 influenza season. Due to tremendous
collaboration among our public health and private sector partners, our
collective ability to modify and enhance our response strategy as
circumstances changed, and the cooperation of the public, I am pleased
to report that we have been successful in our effort to promote and
protect the public's health. We learned valuable lessons from the 2004-
2005 influenza season that are enhancing our planning efforts for the
upcoming influenza season.
Vaccination is the primary strategy for protecting people who are
at greatest risk of serious complications and death from influenza. In
the face of this season's influenza vaccine supply shortage, CDC, state
and local public health officials, vaccine manufacturers and
distributors initiated extraordinary partnership activities to address
this public health challenge. For example, sanofi pasteur (formerly
Aventis Pasteur) provided access to vaccine distribution information to
aid in the allocation of the available vaccine supply to those people
most in need this season. State and local public health officials also
worked closely with CDC to ensure equitable distribution of vaccine to
those areas with the greatest need And we must not forget the important
service of immunization providers on the front lines in doctors'
offices, health clinics, grocery stores, and pharmacies working to
prioritize, deliver, and administer vaccine so that it reaches high-
risk individuals. Together, we found new and effective ways to address
the sudden, late emergence of a substantial influenza vaccine shortage
that had never before occurred.
Despite the challenges presented by the unexpected shortage of
influenza vaccine, CDC immediately responded by changing
recommendations to focus vaccine efforts and then began monitoring the
results of those changes. State specific flu vaccination data for
adults and children were rapidly collected and reported on an ongoing
basis from November 2004 through February 2005. CDC's Behavioral Risk
Factor Surveillance System reported that 62.7 percent of Americans 65
years of age and older reported being vaccinated for influenza between
September 2004 and January 2005. This coverage is comparable to the
percentage of older Americans vaccinated in previous years without
supply shortages. So, many at-risk older Americans were vaccinated as a
result of effective work of state and local health departments and the
cooperation of younger, healthier Americans who ``stepped aside'' to
allow the older and more vulnerable populations to receive vaccine. In
addition, through January of 2005, 48.4 percent of young children
(between 6 and 23 months of age) were vaccinated. This marked the
highest vaccination coverage rate in response to a first-time
recommendation of a new vaccine for children.
preparations for the 2005-06 influenza season
As we prepare for the 2005-2006 influenza season, we are
incorporating into the planning process successful strategies used this
past year. For example, our budget request reflects the need to
strengthen the influenza vaccine supply. Another example is the
inclusion of our state and local public health partners and the vaccine
manufacturers in the planning process for the next influenza season.
Another partnership is the National Influenza Summit, which is
cosponsored by the American Medical Association (AMA) and CDC and has
been meeting annually since 2001. The Summit brings together
stakeholders to discuss issues of concern regarding the annual
influenza season, including vaccine supply. Additionally, throughout
the year Summit partners continue to collaborate to address barriers to
increased influenza vaccinations. This year the Summit will be held May
10-11 in Chicago.
The best strategy for influenza prevention and control both during
annual outbreaks and during a pandemic is vaccination. 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 of those
manufacturers produces its vaccine entirely in the United States.
Anticipating and planning for the next influenza season is an
enormous and complex challenge, involving numerous public health and
private sector entities. The production of influenza vaccine is a
lengthy and complicated process. Six to nine months before the
influenza season begins, manufacturers must predict demand and decide
the amount of the vaccine to produce. Moreover, the onset of the
influenza season, its severity and duration, as well as the potential
public demand for vaccine are highly unpredictable from year to year.
CDC has already begun its planning efforts for the 2005-06
influenza season in anticipation of continued challenges in meeting the
nation's vaccine supply needs. We have established a planning team that
meets almost weekly. The team consists of staff from across CDC, as
well representatives from state and local public health agencies with
input from the National Vaccine Program Office and the Food and Drug
Administration.
To date, CDC has:
Developed possible scenarios for vaccine supply for the coming
season, including the possible disruption of production among
the current influenza vaccine manufacturers for the U.S.
market, the re-entry of Chiron into the market, and the entry
of additional influenza vaccine manufacturers into the U.S.
market;
Worked with the Advisory Committee on Immunization Practices (ACIP)
to develop more refined vaccination priority plans that can be
used should there be another critical vaccine shortage;
Met with U.S.-licensed and other vaccine manufacturers to discuss
their plans for the next season, including production
estimates, and distribution strategies and anticipated time
lines for vaccine availability; and
Worked with sanofi pasteur and other prospective manufacturers and
distributors so that, during the prebooking process, customers
indicate both the total amount of vaccine they need, assuming
an adequate supply, and the number of doses needed to vaccinate
high priority groups in the event of supply limitations.
In addition, CDC is:
Pursuing a vaccine contracting strategy that addresses routine
influenza vaccine purchase and stockpile purchase. We recently
signed contracts for 3.5 million doses maximum of sanofi
pasteur thimerosal-free vaccine, three million doses maximum of
sanofi pasteur multi-dose vials and one million doses of
MedImmune's FluMist. The stockpile doses are being negotiated
now that we have the contracts. The bulk purchase solicitation
is pending.
Monitoring antigen-sparing studies designed to determine if reduced
vaccine dosages can provide sufficient immunity against
influenza, thereby allowing for the protection of more persons
with fewer doses of vaccine.
Developing infection control strategies to prevent the spread of
influenza.
Drafting a written plan highlighting key activities that state and
local public health agencies should consider to prepare for the
upcoming season. This plan is currently being reviewed by our
partners, and we hope to have it finalized before the end of
summer 2005. This will be complemented with a list of key
activities CDC will undertake.
Preparing communication strategies with appropriate messages to
respond to the fluctuations in supply and demand anticipated
throughout the season.
Developing and implementing a plan to evaluate the season.
These comprehensive planning efforts are intended to support the
achievement of important public health objectives, including increasing
the domestic production of influenza vaccine, increasing demand for
vaccine among persons indicated for annual influenza vaccination, and
increasing vaccination coverage, particularly among persons in high-
risk groups, so that we can protect and improve the public's health.
conclusion
Influenza is a serious public health threat, taking the lives of
about 36,000 Americans each year and hospitalizing on average more than
200,000 each year. For this reason, it is imperative that we continue
to refine and improve our capacity to meet any challenges that arise in
terms of vaccine supply, seasonal severity, or other unusual
circumstances. We are applying the lessons learned from the challenging
experiences of the 2004-05 influenza season for this upcoming season
and have established a mechanism to continue to improve and learn in an
effort to assure our nation's citizens are protected from this disease.
Thank you for focusing attention on this important public health
issue and for the opportunity to provide an update on our current
efforts. CDC is committed to protecting and promoting health for all
Americans, preventing disease and disability through public health
research and public outreach, and supporting important public health
interventions, including vaccination. We appreciate your interest in
this issue and your support of CDC's efforts to protect the public's
health.
I will be happy to answer any questions.
Mr. Whitfield. Thank you, Dr. Gerberding.
At this time we recognize Dr. Gellin for his opening
statement.
TESTIMONY OF BRUCE G. GELLIN
Mr. Gellin. Thank you very much, Mr. Chairman and members
of the committee.
I am Dr. Bruce Gellin. I'm the Director of the National
Vaccine Program Office of the Department of Health and Human
Services. I am glad to have the opportunity to speak to you
today about the U.S. influenza vaccination program and the role
of the National Vaccine Program Office, NVPO, in strengthening
the U.S. Influenza vaccine supply.
The NVPO was established in 1988 and has responsibility for
coordinating and ensuring collaboration among the many Federal
agencies involved in vaccine and immunization activities. We
accomplish this by communicating and coordinating with our HHS
agencies as well as with the Department of Defense and the U.S.
International Agency for International Development, and through
our National Vaccine Advisory Committee The development,
production, and delivery of influenza vaccine every year
underscores the complexities of vaccine production itself.
Because they involve living organisms, developing and producing
vaccines poses different challenges than the development and
manufacture of drugs.
In the United States, as with many other countries, the
protection of the population through vaccination depends on
vaccines produced by private companies for profit as well as
for public good. U.S. vaccine manufacturers are faced with
substantial challenges, including the costs and uncertainties
of developing new products, limited returns on investment for
vaccines compared with pharmaceutical products, a regulatory
environment that has very high standards for safety and
effectiveness, concerns about liability issues and, for
influenza vaccine, variable demands from one season to the
next.
Consequently, the number of companies that produce licensed
vaccines for the U.S. Market is small. Each type of vaccine is
made by a limited number of suppliers, as you have already
commented upon; and, in many cases, a single manufacturer
supplies vaccines that we rely on.
Producing the flu vaccine has additional challenges. It is
a vaccine that has to be redesigned and produced every year and
delivered on time to tens of millions of people who desire it
over a several month period in the fall in advance of the
annual flu season. We all witnessed the fragility of the system
last year when one of our two large manufacturers could not
supply vaccine to the market. In recent years, we have also
seen both surges in demand and delays in the delivery of
influenza vaccine creating mismatches between vaccine
availability and enhanced demand, resulting in these de facto
shortages.
While we are optimistic that an increased number of
manufacturers are now interested in the U.S. influenza vaccine
market, presently only three companies are licensed to sell flu
vaccine in the U.S. Two produce an inactivated influenza
vaccine, and a third produces a live-attenuated vaccine that is
delivered by nasal spray.
All U.S.-licensed vaccines are developed from viruses that
are grown in eggs in a process that is unique for influenza
vaccine. In a collaborative effort, both CDC and FDA contribute
to the influenza vaccine manufacturing every year by providing
the vaccine companies with vaccine reference strains, the so-
called seed viruses, as the starting point for a large-scale
manufacturing.
In addition, FDA supplies reagents that set standards for
the manufacturers that determine the vaccine's potency. The
number of vaccine doses produced is limited by the capacity of
the manufacturers' production facilities, the availability of
eggs, the yield of virus growth in the eggs, and the length of
time the manufacturing continues into the season. Although it
is possible for production to continue beyond the summer and
into the fall, there is a substantial risk that late-season
vaccine will go unused since the later vaccine is produced, the
later it will be available to clinics.
Companies need to plan the amount of vaccine that they will
produce well in advance of the flu season so they can secure
the needed egg supply in which the vaccine viruses are grown.
Production of annual flu vaccines takes about 6 to 9 months,
and any disruption in the production schedule for any reason
may lead to a delay in the availability of the vaccine.
Influenza vaccine supply issues are also critical for
pandemic influenza preparedness since the pandemic vaccine
supply is directly related to existing influenza vaccine
manufacturing capacity. Many experts believe that the risk of a
flu pandemic or a global epidemic is higher now than it has
been in the past because of the spread of avian influenza in
wild and domestic bird species across Asia. Since January 2004,
89 people, mostly young and otherwise healthy, have been
confirmed by the World Health Organization to have been
infected with the H5N1 virus, and 52 of them have died. And we
heard of a new case reporting a death from Cambodia just this
morning from the World Health Organization. The people who died
were known to have died of this infection. We are concerned
that should this virus develop the capacity to be easily
transmitted among humans, either through a mutation or mixing
genes with a human flu virus, a pandemic could result.
Ensuring the ability to meet current annual demand for flu
vaccine, to improve prevention of influenza disease, and to
prepare for a pandemic all require strengthening the flu
vaccine supply in the U.S. Building on the response to the flu
vaccine shortage last year, NIH and FDA have worked to
facilitate the clinical evaluation of a flu vaccine produced by
GlaxoSmithKline and to expeditiously develop the data base
necessary to allow the company to apply for FDA approval in the
coming influenza season.
Several additional HHS flu vaccine initiatives have been
put in place to address our pandemic preparedness needs and
will also help to achieve our annual influenza prevention goal.
The objective of these initiatives are to secure and expand the
U.S. influenza vaccine supply, diversify production methods,
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 President's fiscal year
2006 budget includes an additional $120 million to further
strengthen this component of overall pandemic influenza vaccine
preparedness.
To enhance our Nation's ability to produce influenza
vaccine at any time during the year, we issued a contract with
Sanofi-Pasteur of Swiftwater, Pennsylvania, for $41 million.
This has allowed the company to change the way it manages eggs,
and they have already begun to change its flock management
strategy to ensure that eggs are available year-round for the
vaccine.
Diversification of flu vaccine production methods will also
help to strengthen our system. Cell culture technology is a
well-established vaccine production method for other vaccines
such as the inactivated poliovirus, and two companies have
registered their cell culture flu technology in Europe. This
technology does not require eggs as a substrate, thereby
avoiding the vulnerabilities associated with an egg-based
production system.
Secretary Leavitt announced last month that HHS issued a 5-
year contract 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 such a
vaccine. Under this advanced development contract, the company
has also committed to develop a plan to manufacture this
vaccine at a U.S.-based facility that has the capacity to
manufacture 300 million doses of monovalent vaccine over a 1-
year period.
We have three additional areas where we believe strategic
investments will move us toward achieving the annual and
pandemic influenza supply goals. In addition to providing
support for cell-based vaccines, we hope to further diversify
vaccine technology by supporting recombinant pandemic influenza
vaccines. We also are going to invest in production technology
that will increase the efficiency of manufacturing and planing
to support research and development of strategies that will
stretch the number of vaccine doses produced by decreasing the
amount of flu virus antigen that is needed in each dose.
While these are only the first steps 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.
Thank you for your attention to this topic, and I look
forward to your questions. 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
Chairman and members of the Committee, I am Dr. Bruce Gellin and I
am the Director of the National Vaccine Program Office of the
Department of Health and Human Services. I am pleased to appear before
you today to discuss the U.S. influenza vaccination program and the
role of the National Vaccine Program Office (NVPO) in strengthening
U.S. influenza vaccine supply.
The National Vaccine Program Office was established in 1988 to
improve prevention of disease through vaccination and to improve
prevention of vaccine associated adverse events. NVPO has
responsibility for coordinating and ensuring collaboration among the
many federal agencies involved in vaccine and immunization activities.
We have addressed this mission by communicating and coordinating with
HHS' agencies, the Department of Defense and the US Agency for
International Development, and through the National Vaccine Advisory
Committee.
NVPO's mission is to:
Coordinate and integrate activities of all Federal agencies involved
in immunization efforts;
Ensure that these agencies collaborate, so that immunization
activities are carried out in an efficient, consistent, and
timely manner;
Develop and implement strategies for achieving the highest possible
level of prevention of human diseases through immunization and
the highest possible level of prevention of adverse reactions
to vaccines; and
Ensure that minimal gaps occur in Federal planning of vaccine and
immunization activities.
The development, production and delivery of influenza vaccine every
year underscores the complexities of vaccine production. Because they
involve living organisms, developing and producing vaccines poses
different challenges than drugs. In the United States, the protection
of the population through vaccination depends on vaccines produced by
private companies for profit as well as for public good.
U.S. Vaccine manufacturers are faced with substantial challenges
including the costs and uncertainties in developing new products,
limited returns on investment for vaccines compared with other
pharmaceutical products, a regulatory environment that has high
standards for safety and effectiveness, concerns about liability
issues, and variable demand from one influenza season to the next.
Consequently, the number of companies that produce licensed vaccines
for the U.S. market is small and each type of vaccine is made by a
limited number of suppliers. In many cases vaccines that we rely on in
the U.S. are supplied by a single manufacturer.
Producing influenza vaccine has additional challenges. It is a
vaccine that has to be redesigned and produced each year and delivered
on-time to provide protection to tens of millions of people over a
several month period in the fall in advance of the annual influenza
season. The fragility of this system was clearly documented during the
past influenza season, when one of the two large influenza vaccine
manufacturers could not supply vaccine to the U.S. market. Recent years
also have seen surges in demand and delays in the delivery of influenza
vaccine creating mismatches between vaccine availability and enhanced
demand resulting in de facto shortages.
While we are optimistic that an increased number of manufacturers
are interested in the U.S. influenza vaccine market by, presently only
three companies are licensed to sell influenza vaccine in the U.S.; two
produce inactivated influenza vaccine while the third produces a live-
attenuated vaccine that is delivered by nasal spray. All U.S. licensed
influenza vaccines are developed from viruses that are grown in
embryonated eggs in a process unique for influenza vaccine. Because of
the tight time lines to produce influenza vaccine, the influenza
vaccine manufacturers begin production of the following season's
vaccine even before the FDA's Vaccine and Related Biological Products
Advisory Committee meets in mid-February to review global influenza
surveillance data and officially select the components--the virus
strains--that are projected to be the predominant strains circulating
in the U.S. during the following season. Both CDC and FDA contribute to
influenza vaccine manufacturing by providing vaccine companies with
vaccine reference strains--so-called ``seed viruses''--as the starting
point for large scale manufacturing In a rotating fashion, each of the
three vaccine virus strains selected for the following year's vaccine
composition are adapted to grow in eggs and are injected separately
into millions of fertilized eggs, which are subsequently incubated to
allow the influenza virus to grow. These egg-grown viruses are
subsequently inactivated, purified, tested for potency, blended into
the trivalent vaccine, and filled into syringes or vials. The number of
influenza vaccine doses produced is limited by the capacity of the
production facilities, the availability of embryonated eggs, the yield
of influenza virus from each egg, and the length of time that
manufacturing continues. Companies need to plan the amount of vaccine
they will produce well in advance of the influenza season so that they
can secure the needed egg supply in which vaccine viruses are grown.
Production of annual influenza vaccines, which contain three different
influenza viruses, takes about six to nine months. Any disruption of
the production schedule may lead to a delay in vaccine availability.
Annual variation in the timing and severity of influenza outbreaks has
resulted in significant fluctuations in demand for vaccine so that in
some years supply is tight while in others, millions of vaccine doses
go unused. Although it is possible for production to continue beyond
the summer and into the fall, there is a substantial risk that late-
season vaccine will go unused since the later vaccine is produced; the
later it will be available to the clinics. Traditionally there has been
little interest in ``late season'' vaccination--which in the United
States is around Thanksgiving. .
Thus, the current fragility in influenza vaccine supply largely is
related to:
A limited number of U.S.-licensed manufacturers
Uncertainty regarding annual demand and the ability to sell all
vaccine produced
An inability to stockpile trivalent vaccine for longer than a year
due to annual changes in the influenza viruses that circulate
and cause disease such that vaccine not used in one season is
generally not useful the following year
A solely egg-based production system that has limited flexibility and
surge capacity
Financial and other barriers, to development and U.S. licensure of
new influenza vaccines, and
Limited interest by most of the public and health care community in
providing ``late season'' vaccination
The limitations and disruptions of influenza vaccine supply also
must be put within the context of continued high rates of mortality and
morbidity each year from influenza disease and the need to improve our
prevention program. In 2004, Acting Assistant Secretary for Health, Dr.
Beato, asked the National Vaccine Advisory Committee (NVAC) to assess
the influenza prevention program and to make recommendations on how
this program could be improved. NVAC recommendations to strengthen
influenza disease prevention included:
Improving our understanding of influenza vaccine demand--and why so
many of those for whom annual influenza vaccine is recommended
do not get vaccinated (e.g., persons > 65 years of age,
pregnant women and even health care workers),
Reviewing the evidence that would support further expansion of the
groups recommended for annual vaccination;
Implementing systems to better track the burden of influenza illness
and the effectiveness of the vaccination program; and,
Conducting a thorough review of the Department's influenza research
program to identify gaps, and strengthening of cross-Department
collaboration.
A sufficient and secure influenza vaccine supply is a prerequisite
if we are to implement these recommendations and improve influenza
disease prevention by increasing vaccination coverage and expanding
groups recommended for vaccination.
Influenza vaccine supply issues also are critical for pandemic
influenza preparedness since the pandemic vaccine supply is directly
related to existing influenza vaccine manufacturing capacity. Many
experts believe that the risk of an influenza pandemic--or global
epidemic--is higher than it has ever been in the past because of the
spread of avian H5N1 influenza in multiple wild and domestic bird
species across much of Asia. Since January 2004, 88 people, mostly
young and otherwise healthy, have been confirmed by the World Health
Organization to have been infected with the H5N1 influenza virus, and
nearly two out of three of people who are known to have been infected
have died as a result of this infection. Should this virus develop the
capacity to be easily transmitted among humans, either through a
mutation or by mixing genes with a human influenza virus, a pandemic
could result. Because H5 influenza viruses have not previously spread
among people, the entire global population would be susceptible
We are all keeping a watchful eye on the current situation in Asia
while at the same time recognizing that, in recent years, there also
have been outbreaks of avian influenza infections and sporadic human
cases caused by other influenza virus subtypes originating in Europe
and in Canada as well as in Asia. A pandemic can unpredictably occur,
could be caused by an influenza subtype other than H5, and could
originate in any country.
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 of an influenza vaccine produced by
GSK and to expeditiously consider a licensure application such that
this influenza vaccine may potentially be licensed for the upcoming
season.
Several additional HHS influenza vaccine supply initiatives have
been put in place to address pandemic preparedness needs and will also
help to achieve 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. To enhance our Nation's
ability to produce influenza vaccine at any time during the year, 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 already 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 with the doses being delivered later in
the fall.
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. Additionally, cell culture
technology uses a closed system that dramatically reduces the
possibility for contamination. Finally, the new cell-based influenza
vaccines 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 also has committed to develop a plan
to manufacture 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.
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. This
contract, which we hope will lead to the licensure and U.S. production
of a next generation influenza vaccine, will further increase
production capacity and diversification of the manufacturing base.
Whereas building new influenza vaccine production facilities is an
intermediate approach to expand the influenza vaccine supply, other
strategies are more short term and expand the current vaccine capacity
by increasing the efficiency with which influenza vaccine doses are
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. A second RFP will
be issued this spring and will support improvements of the
manufacturing process to increase overall influenza vaccine production
at current manufacturing facilities.
The third RFP that will be issued is to 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 it's administered, you may be
able to 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 would be significantly increased. 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 immune
cells are located. Both strategies have been evaluated in clinical
trials and have the potential to expand influenza vaccine supply
several-fold.
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.
Thank you for your attention to my remarks this morning--and more
importantly to the attention that you have paid to the prevention and
control of annual and pandemic influenza.
I would be happy to answer any questions from the Committee.
Mr. Whitfield. Thank you.
Dr. Goodman, you are recognized for 5 minutes.
TESTIMONY OF JESSE L. GOODMAN
Mr. Goodman. Thank you, Mr. Chairman.
Mr. Chairman and members of the committee, I am Jesse
Goodman. I am the Director of the Center for Biologics,
Evaluation and Research for the FDA. I am also an infectious
disease physician. I appreciate the opportunity to update you
on our readiness efforts for the 2005 and 2006 and future flu
seasons, and I am actually pleased to report continuing
progress. I also want to assure the American public and
yourselves that the safety, effectiveness, and availability of
vaccines are among FDA's highest priorities.
Talking first about last season, flu vaccine is highly
cost-effective and beneficial to the public, as many of you
have emphasized. However, also, as we have emphasized in
previous testimony, flu vaccine manufacturing is particularly
complex and challenging, and the market is also very fragile,
in part because of our successes. Increases in demand have been
coupled by a decline in the number of manufacturers. As Dr.
Burgess happened to mention also, this is something that we see
in other sectors of the vaccine industry.
As you know, in October 2004, the British regulatory
agency, the MHRA, suspended the license of Chiron, and FDA also
concluded that the safety of the vaccine Chiron produced for
2004 could not be assured.
Now, I want to say that as soon as we learned this, really
within hours, FDA worked with great urgency and in close
collaboration with HHS and CDC and other components and with
the private sector. We engaged them very quickly, and we
obtained 5 million additional doses of U.S.-licensed vaccine,
and this increased the supply last year to 61 million doses.
We were still concerned that needs could outstrip supply,
particularly if we had a significant flu season, so we sought
additional vaccine licensed in other countries with quality
regulatory agencies that might be made available as
investigational new drugs urgently. FDA immediately sent teams
to the facilities of such potential sponsors. Our staff
carefully evaluated their manufacturing processes and reviewed
a large volume of manufacturing clinical data, and this was all
done within just a few weeks. These efforts resulted in INDs
that could have permitted the use of approximately 4 million
doses of GlaxoSmithKline's vaccine and 1 million doses from
Berna Biotech if they were needed.
The interactions with these and, in fact, other
manufacturers have provided valuable information that is
helping us now. They have stimulated interest in a number of
companies in pursuing U.S. Licensure, and this is at least one
constructive outcome of the challenges we all faced last year.
I am very proud of the efforts and accomplishments of more than
50 FDA professionals as well as many HHS colleagues in working
collaboratively for long hours on these challenges.
Well, what are we doing going forward? We, too, the last
thing we want to see is this problem recur, whether it is this
year or the future years, and we need to work both for this
year and for future years. We are doing everything we can to
improve flu vaccine for this coming season and in future years,
and we are taking a dual-track approach.
First, because Chiron's correction of its manufacturing
processes is a major factor, FDA is doing all we can to
facilitate that effort. As Ms. Schakowsky alluded to the
problem of information sharing, agreements have been put in
place with both Chiron and MHRA that have allowed full sharing
of information, and this has been extremely productive. FDA and
MHRA collaborative reviewed Chiron's remediation plans, and
these are extensive plans, and are providing ongoing feedback
as they are implemented and as manufacturing activities
startup. So this is a very rich, interactive relationship.
FDA and the MHRA, the British regulators, are working
closely together and actively communicating also on
inspectional activities. We accompanied MHRA on inspections of
Chiron Liverpool in December of 2004 and again in February. We
are continuing to coordinate with them on these inspectional
efforts and plan a joint effort again right now; one is in the
planning stages for the upcoming time period.
As a result of a great deal of progress at the Liverpool
facility, as most of you know, the British regulators, MHRA,
lifted its license suspension on March 2, 2005, allowing Chiron
to proceed with manufacturing. To get an updated overview of
some of these ongoing efforts, last week I met with MHRA
leadership in London and I also visited Chiron's Liverpool
facility to meet with their senior leadership team onsite.
Chiron reported to me on their progress and specifically their
progress in addressing the issues of concern including changes
made at their facility, changes in their manufacturing process,
and improvements in their quality systems.
Once Chiron has completed implementation of its key
remediation measures and the critical stages of manufacturing
are in full swing and can therefore be adequately evaluated,
likely in the late spring or early summer, FDA will conduct its
comprehensive inspection to assure that Chiron has adequately
addressed its problems.
It is too early to predict the final outcome of Chiron's
remediation activities, but, nonetheless, I can say the company
has made significant progress in a short time. However, there
are great demands in applying the necessary changes that have
been made to full-scale manufacturing in a very tight
timeframe. So this is the challenge that remains.
Because of this, and because of the long-term issues that
we have all discussed, FDA is simultaneously working on a
second track. That track aims to facilitate greater capacity
and diversification, an issue raised by Ms. DeGette, in the
U.S. influenza vaccine supply. It is important to emphasize,
though, that the demand for vaccine--the demand for the vaccine
and other economic issues are really the primary factors here
that determine whether a manufacturer will seek and maintain a
license in a country, including the U.S., the strength of the
manufacturing infrastructure in the United States, and the
amount of vaccine that a manufacturer will decide to produce.
Some of the developments in those areas right now, Sanofi-
Pasteur, as you know, has indicated that it can produce the
same or more doses of its vaccine for the coming flu season.
MedImmune plans to produce a similar amount of vaccine and is
also performing studies that, if successful, may allow future
further use of its vaccine in future years in additional age
groups.
FDA, as Dr. Gellin mentioned, has informed manufacturers
that it will consider new approaches to influenza vaccine
licensing, such as accelerated approval based on surrogate
markers like the antibody response that are likely to predict
benefit. GlaxoSmithKline, as a result, has stated that in the
near future it expects to submit a license application to FDA
seeking accelerated approval of this influenza vaccine and
that, if licensed, it should be able to supply 10 million doses
for the 2005 to 2006 season.
But also we have challenged ourselves to identify other
lessons learned, something identified by Congresswoman Baldwin,
from this past year's influenza season to do whatever we can
from our end to help prevent similar future problems. One that
many of you are aware of is that we are now conducting
inspections of flu vaccine manufacturers on an annual basis.
This can't solve all problems, we can't manufacture the vaccine
for them, but what it may do is allow earlier recognition and
intervention, and perhaps in a preventive mode, when problems
occur. We have completed additional information-sharing
agreements with numerous foreign regulatory agencies focusing
on ones where flu and other critical vaccine information
sharing is important.
Finally, again mentioned by Dr. Gellin, in terms of the
pandemic preparedness, we are extremely actively engaged with
sponsors and manufacturers who are interested in developing new
technologies, including cell-culture-based and recombinant
vaccines. Although a lot of work remains to be done on these
technologies, they provide important alternatives to egg-based
production, and they may help reduce the time requirements and
certain risks of contamination inherent in egg-based
production.
So, to conclude, we are doing everything we can in
conjunction with other public health service agencies and
industry to enhance the availability of flu vaccine both now
and in the future. An adequate vaccine supply supplemented by
effective antivirals can greatly decrease our vulnerability and
provide protection against influenza. All the steps we have
discussed will not only help protect Americans from flu every
year but can help strengthen our infrastructure and its
capacity and better prepare us for a pandemic, and we welcome
the opportunity to work with you in Congress to accomplish
these important health goals. So I thank you for having me to
discuss this important issue, and I am happy to participate in
answering your questions.
Thank you.
[The prepared statement of Jesse L. Goodman follows:]
Prepared Statement of Jesse L. Goodman, Director, Center for Biologics,
Evaluation and Research, Food and Drug Administration, U.S. Department
of Health and Human Services
introduction
Mr. Chairman and members of the Committee, I am Dr. Jesse Goodman,
Director of the Center for Biologics Evaluation and Research (CBER) at
the Food and Drug Administration (FDA) and also a practicing infectious
diseases specialist. I appreciate the opportunity to update you on
FDA's recent and ongoing efforts, in collaboration with other
Department of Health and Human Services (HHS) agencies and with the
private sector, to address issues surrounding the influenza vaccine
supply needs for the next flu season and to do what we can to help
prevent the problems encountered last season from recurring. These
efforts should also better prepare us for the next global influenza
pandemic.
FDA is responsible for the regulation and oversight of vaccines in
the United States. Vaccines are among our most important and cost-
effective medical interventions, preventing disease in those who
receive them and reducing the spread and risk of infections through our
communities. I want to assure the American public that the safety,
effectiveness and availability of vaccines are among FDA's highest
priorities and that we work closely with DHHS, the Centers for Disease
Control and Prevention (CDC) and the National Institutes of Health
(NIH), as well as with manufacturers, in addressing this important area
of public health preparedness.
the 2004-2005 influenza season
As you know, influenza vaccine is unique because its active
ingredients--the virus strains used to develop the vaccine--change
almost every year. Therefore, manufacturers must produce tens of
millions of doses of a new vaccine each year. While promising
technologies such as cell culture and recombinant protein and DNA-based
influenza vaccines are in the research and development stages and we
are working with our HHS colleagues to advance their development, the
most efficient vaccine production methods currently available involve
the use of millions of live, non-sterile eggs to grow three different
strains of influenza viruses annually. This is a complex process that
spans several months during which manufacturers cultivate the
appropriate strains to make the vaccine. These factors present an
enormous challenge for manufacturers and create uncertainty for vaccine
supply.
Each year, FDA begins working with manufacturers at the earliest
stages of vaccine development, and we continue to assist them
throughout the production phase. We do this not only through our
regulatory evaluations, but also by providing needed influenza strains
and standards that can be used for efficient manufacturing.
Specifically, we provide reagents to assure that the vaccine is potent
and we further evaluate the vaccine through the use and review of
laboratory tests that help assure the safety and efficacy of the
vaccine. Throughout this process, FDA frequently discusses technical
and manufacturing issues with manufacturers.
Influenza vaccine is highly cost-effective and beneficial to the
public. Over the last decade, health care providers, CDC and others
have been very successful in expanding the number of Americans who
receive the vaccine. However, as we have emphasized in previous
Congressional testimony, the influenza vaccine market is very fragile
because the increasing demand has been coupled with a decline in the
number of U.S-based and U.S.-licensed manufacturers. Importantly, the
market returns for producing this and many other vaccines are usually
minimal, while the financial and other risks involved are great.
Further, vaccine manufacturing requires careful and comprehensive
controls, a complex and sometimes unpredictable manufacturing process
and highly specialized facilities that can be expensive to maintain and
update. For the 2004-2005 season, only three U.S. licensed
manufacturers began production of influenza virus vaccine: Chiron
Corporation and aventis pasteur produced inactivated vaccine, the form
currently used for most high-risk individuals, while MedImmune, Inc.
manufactured FluMist, a recently-approved, live, attenuated (weakened
and safe) influenza vaccine.
As you know, on October 5, 2004, the United Kingdom's Medicines and
Healthcare products Regulatory Agency (MHRA) suspended Chiron's license
to manufacture influenza vaccine due to good manufacturing practice
deficiencies that led to sterility failures in filled vials of the
vaccine. FDA and MHRA's review of Chiron's investigation of the root
cause of the company's sterility failures and our own review and
inspections of their facility pointed to problems that led FDA to the
conclusion that the sterility, and therefore safety, of the vaccine
Chiron produced for the 2004-2005 influenza season could not be
assured.
Efforts to Obtain Additional Vaccine
The loss of Chiron's planned contribution to the U.S. influenza
vaccine supply posed serious challenges. FDA worked with urgency,
aggressiveness and in close coordination with CDC and other components
of HHS and the private sector to explore all viable options to secure
additional doses. FDA worked with sanofi pasteur and MedImmune to
secure approximately five million additional doses of U.S. licensed
vaccine. Sanofi pasteur increased production to 58 million doses of
Fluzone, and MedImmune scaled up to produce three million doses of
FluMist. FluMist is currently recommended for healthy individuals 5 to
49 years of age, and therefore provides an option for those who would
not receive vaccine under CDC's priority guidelines, such as the U.S.
military. Therefore, to expand further the supply of vaccine to those
with the greatest need, then-Secretary Thompson, in cooperation with
the Department of Defense, announced that the military would maximize
its use of FluMist as a substitute for inactivated vaccine, making an
additional 200,000 doses of injectable vaccine available to HHS for
high-risk civilian populations. Because sanofi pasteur produces
pediatric dosage forms of vaccine for the U.S. market, the supply of
vaccine available for high-risk children was, fortunately, not reduced.
Through these collaborative efforts, manufacturers increased the
available supply of licensed influenza vaccine for the U.S. population
to 61 million doses for this past influenza season, compared with
approximately 83 million doses distributed in 2003-2004 and in 2002-
2003, 77 million doses in 2001-2002 and 70 million doses in 2000-2001.
Because there was a concern that the need and demand could still
outstrip supply, particularly if we faced a severe influenza season, we
sought additional doses of vaccine that could be safely used in an
emergency. Thus, in addition to enhancing the supplies of vaccine
approved for use in the U.S., we were able to rapidly identify
suppliers of approximately five million doses of additional vaccine,
licensed in other countries, which could potentially be made available
under an FDA investigational new drug (IND) application. With
remarkable cooperation from several companies and from other regulatory
agencies (including the Paul Ehrlich Institute, Germany; Therapeutic
Goods Administration, Australia; Swiss Medic and Health Canada) FDA
immediately sent inspectors and scientists to the manufacturing
facilities of potential IND sponsors to evaluate their manufacturing
processes. Coupled with these efforts, we also reviewed a large volume
of manufacturing and clinical data, all within a few weeks. These
efforts resulted in INDs that would have permitted the use of
approximately four million doses from GlaxoSmithKline (GSK) and one
million doses from Berna Biotech, had they been needed. HHS and FDA's
coordinated interactions with these and other influenza vaccine
manufacturers and regulatory agencies also provided valuable
information and strengthened relationships that helped stimulate
interest by additional influenza vaccine manufacturers to pursue U.S.
licensure. This is one constructive outcome of the challenges we faced
this past flu season. I am very proud of the efforts and
accomplishments of more than 50 FDA employees, from multiple offices,
as well as our HHS and CDC colleagues, working collaboratively for long
hours to help meet this public health challenge.
Efforts to Enhance Antiviral and Pneumococcal Vaccine Supplies
Following the loss of the Chiron vaccine, FDA also contacted
manufacturers worldwide in an effort to identify additional supplies of
antiviral medications that could be used, if needed, for treatment of
millions of influenza cases and for prevention in high-risk individuals
in epidemic settings.
Serious morbidity and mortality from influenza is often due to the
complication of bacterial pneumonia. In particular, pneumococcal
pneumonia is one of the most common serious complications of influenza
in high-risk individuals. This complication is preventable through use
of an inexpensive, yet underutilized, pneumococcal vaccine. The
influenza vaccine shortage provided an impetus to increase the
availability of vaccine against pneumonia. In cooperation with HHS,
Merck & Company tripled its production of its pneumococcal
polysaccharide vaccine from 6 million to more than 17 million doses.
The beneficial effects of pneumococcal vaccine last for five to ten
years, and CDC and other public health agencies strongly encourage its
use.
plans for 2005 and future years
At the same time that we have addressed the past year's shortage by
facilitating the availability of additional vaccine, antivirals, and
pneumococcal vaccine, we are doing everything we can to help improve
supply for future years. We are applying a dual-track strategy.
First, the most important single factor that will affect the status
of the U.S. influenza vaccine supply for the coming year will be
whether Chiron can correct its manufacturing problems at the Liverpool
facility and supply vaccine for the U.S. market. To succeed, Chiron
must implement extensive improvements needed to satisfy both FDA and
the U.K. regulatory authority. We have come a long way since October 5,
2004, when MHRA could not legally communicate with FDA about its
pending enforcement action.
After MHRA's suspension of Chiron's license to manufacture
influenza virus vaccine at the Liverpool facility, Chiron gave MHRA and
FDA permission to discuss information that could not otherwise be
shared. This arrangement allowed free exchange of information as the
company initiated efforts to address the problems at Liverpool. Then,
on February 14, 2005, FDA signed a general information-sharing
agreement with MHRA that, among other things, permits advance
communication on important issues and not limited to Chiron's influenza
vaccines. Chiron developed an extremely comprehensive remediation plan
which has been undergoing implementation during recent months. FDA and
MHRA reviewed and provided extensive input on this plan and the Agency
continues to provide extensive feedback to both Chiron and MHRA.
FDA and MHRA are also working together and actively communicating
on inspectional activities. For example, FDA accompanied MHRA on
inspections of the Chiron Liverpool facility in December 2004 and
February 2005, and has had very frequent interactions with both Chiron
and MHRA concerning implementation of the remediation plan and start up
of manufacturing activities. As a result of progress in the Liverpool
facility, MHRA lifted its license suspension on March 2, 2005, which
has allowed Chiron to proceed with manufacturing plans. FDA is
continuing to interact intensively with both MHRA and Chiron as the
company further institutes its remediation plan and begins to gear up
for manufacturing.
FDA will continue to coordinate with and accompany MHRA on future
inspections--one of which is currently in the planning stage. FDA will
continue to provide MHRA and Chiron with feedback and information. Once
Chiron has implemented all key remediation measures and critical stages
of manufacturing are in full swing (likely in late Spring or early
Summer), FDA will conduct a complete and comprehensive inspection of
Chiron's Liverpool facility to verify that Chiron has adequately
addressed its problems. Our continuing interactions with Chiron
indicate the significant progress that has been made in a short period
of time, but it is also clear that full scale manufacturing and all its
associated challenges remain and will require continuing intensive
efforts that will need to succeed under very tight time frames. Only
after passing MHRA and FDA inspections will Chiron be able to provide
vaccine for the U.S. market. Chiron's vaccine will have to meet all
FDA-required standards, including sterility and other safety testing,
prior to distribution to the public. While it is too early to predict
the outcome of Chiron's remediation activities, Chiron is making
continuing progress toward its goal of being able to supply vaccine for
the US market for the upcoming season.
While working hard to facilitate Chiron's efforts to correct its
manufacturing problems, FDA is also working on a second track to
improve preparedness for this and future influenza seasons and
facilitate greater overall capacity and diversification of the U.S.
influenza vaccine supply. It is important to recognize, however, that
demand for vaccine and other economic factors are, and will, remain the
primary factors that determine 1) whether a manufacturer will seek and
maintain licensure, 2) the strength of the manufacturing infrastructure
in the U.S., and 3) the amount of vaccine that manufacturers produce
for the U.S. market. These factors also apply to other vaccines and the
U.S. vaccine supply infrastructure in general. CDC and FDA are working
to encourage extending vaccination throughout the flu season, including
January and February. If such demand exists, manufacturers can increase
total doses available by producing vaccine that becomes available
during these months. Because influenza cases usually continue or peak
well after the November-December time period when most people seek
immunization, continuing vaccination is beneficial to recipients and
should be encouraged.
MedImmune is performing studies that, if successful, may support
future use of its vaccine in additional age groups. MedImmune has also
stated that, if successful, it should be able to produce additional
vaccine to support those needs. Sanofi pasteur has indicated that it
has the capability to produce the same or more doses of Fluzone for the
2005-2006 influenza season as it did in 2004-2005. Greater influenza
vaccine production capacity and an increase in vaccination rates are
also critical for improving our preparedness for a global pandemic. In
the event of a pandemic, we would need the capacity to rapidly produce
a new vaccine and make it available to all who need it.
While greater production by currently-licensed manufacturers will
enable us to meet some of these needs, recent events highlight the
potential benefits of having more U.S.-licensed manufacturers. In
recognition of this, FDA has been doing everything possible to
stimulate interested foreign-licensed manufacturers to provide or,
where needed, develop the safety and effectiveness data required for
U.S. licensure. FDA has interacted constructively with several
interested firms in this regard. FDA has informed manufacturers that it
is willing to consider new approaches to influenza vaccine licensing,
such as accelerated approval based on likely surrogate markers (e.g.
the degree of antibody response to the vaccine), followed by post-
licensure clinical effectiveness evaluation. The National Institute of
Allergy and Infectious Diseases (NIAID) supported clinical studies of
GSK's influenza vaccine. Thanks in part to that research, GSK has
stated that it expects to submit the needed data to FDA to seek
accelerated approval of its influenza vaccine for the U.S. market in
the near future. GSK has stated that if its vaccine is licensed, it
expects to be able to supply 10 million doses of vaccine in time for
the 2005-6 season. ID Biomedical of Canada has also indicated interest
in seeking accelerated approval for its influenza vaccine. It has
stated that it expects to complete needed studies and submit a license
application in 2006 and that, if licensed, vaccine would potentially be
available in time for the 2006-7 season.
So, in preparation for the upcoming influenza season, we are
continuing to do everything we can to facilitate both Chiron's
remediation and GSK's licensure efforts so that these vaccines can
potentially be available to help meet the 2005-6 flu season's needs. In
either case, potential difficulties should become apparent during the
summer. If it becomes necessary to obtain additional vaccine for use
under an IND, the experience and relationships built this year through
reviewing and obtaining vaccines licensed by other regulatory
authorities will be helpful.
other important activities
We have challenged ourselves to identify other lessons learned from
this past year's influenza season and to examine how we can use our
recent experience to help prevent similar problems in the future. For
example, as I previously mentioned, we have identified the need to
allow free flow of information between FDA and our international
regulatory counterparts, and vice versa. We committed to do so and have
now completed confidentiality commitments that allow such information
sharing with regulatory agencies in the UK, Australia, Canada, the
European Commission, Japan, Mexico, Switzerland, Singapore, and South
Africa. We are also in final negotiations on an agreement with New
Zealand. We are undertaking discussions with several additional
European countries where vaccine manufacturing important to U.S. public
health takes place. In addition, we are continuing to inventory foreign
manufacturing to identify any additional information-sharing needs. We
also plan to seek agreements with other national regulatory authorities
where necessary. These commitments will help assure that legal barriers
do not inhibit critical communication between these agencies and FDA.
As in past years, FDA will work closely with CDC, WHO and others to
develop materials for standardization and evaluation of influenza
vaccine for the 2005-2006 flu season. FDA will continue to identify and
evaluate influenza virus strains suitable for manufacturing purposes
and provide to manufacturers the high growth reassortant viruses they
need to help to facilitate efficient, timely and adequate production of
vaccine.
Recent events highlight the importance of FDA's technical support
for the U.S. and global vaccine manufacturing infrastructure and the
need for manufacturers to invest in more efficient, reliable and modern
methods for producing influenza vaccine. With adequate supply and
widespread immunization, we will be more likely to meet the challenge
of annual influenza epidemics and future pandemics.
CBER has also initiated a vulnerability analysis of foreign
manufacturing of U.S. licensed products that are critical to U.S.
public health. This analysis will include other vaccines and help to
identify areas where consideration of actions to support supply may be
needed, such as stockpiling or seeking additional licensed
manufacturers. In addition, in the hope that more vaccines can be
licensed and available to multiple regions of the world, FDA has been
working with our foreign regulatory counterparts and with manufacturers
to enhance international communication with the goal of more efficient
product development. We are also encouraging development of scientific
and regulatory standards for safety, potency and effectiveness that
will help achieve these goals. FDA serves as a designated Collaborating
Center of the World Health Organization (WHO), and we work closely with
our sister agencies at HHS and WHO on pandemic preparedness and
responding to other emerging infectious diseases.
Under FDA's Critical Path initiative, we are working
collaboratively with HHS agencies and the private sector to facilitate
the rapid development, evaluation and availability of medical products
and related manufacturing, safety and effectiveness standards. The
rapid development and implementation of a West Nile Virus screening
test for the blood supply provides a good example of the effectiveness
of this type of a collaborative public-private approach to meet the
threat of emerging infections.
To help manufacturers overcome challenges such as the problems
Chiron is experiencing, FDA, under its current Good Manufacturing
Practice for the 21st Century initiative, is working with industry to
encourage the use of advanced technologies, quality systems and risk-
based approaches that build quality into the manufacturing process. FDA
is also using the same quality systems and risk-based approaches to
modernize its manufacturing-related regulatory responsibilities.
Recognizing that clarity and quality in vaccine GMPs is of increasing
importance, CBER has planned increasing outreach in this area for the
coming months, including international workshops and meetings.
The experiences of the past six months have taught us important
lessons about manufacturing and inspectional activities with respect to
influenza vaccine. The annual changes in the flu vaccine and the
increased dependence on a smaller number of manufacturers highlight the
risks of unexpected manufacturing difficulties. For these reasons, in
2005 and the future, we plan to inspect influenza vaccine manufacturers
annually. Further, while FDA has always interacted extensively with
influenza vaccine manufacturers throughout the vaccine production
cycle, we plan additional interactions, including foreign regulatory
agencies where appropriate, based on findings or events that raise
concerns.
pandemic preparedness
HHS is working to help transform the influenza marketplace and
reinvigorate the influenza vaccine infrastructure by investing in
promising new technologies, securing additional licensed vaccines and
medicines and preparing stronger response plans and capacity.
Furthermore, the lessons we have learned and insights gained from
recent experiences with influenza vaccine are critical in preparing for
an influenza pandemic. This is something that FDA and others in the
public health community are very concerned about, given the eventual
likelihood of a pandemic and the recent outbreaks of avian influenza in
Asia. More widespread vaccination during periods between pandemics not
only has direct health benefits but also will increase vaccine
production capacity and help America and the global community better
prepare for an influenza pandemic.
As part of HHS' efforts to support pandemic preparedness, NIAID
contracted for the production of pilot lots of potential pandemic
vaccines from two licensed U.S. manufacturers. HHS contracted for the
production of two million doses of vaccine against H5N1 avian flu, the
influenza type of current concern in Southeast Asia. NIAID recently
initiated critical clinical studies of the first H5N1 vaccine under
INDs that FDA oversees, and both agencies will be working together to
evaluate the results. While much work remains, these steps to produce
and evaluate pandemic influenza vaccines are a critical component of
our preparedness efforts. They will inform us about the needed dosing
and schedule of pandemic vaccine and help pave the way for evaluation
and potential licensure and broader use of a vaccine against avian flu
if needed.
In addition, NIH and FDA support studies to develop vaccine
strategies that could lead to longer-lived immunity and the production
of an immune response that could potentially allow one year's vaccine
to better provide immunity for multiple flu seasons. FDA is actively
engaged with sponsors and manufacturers interested in developing new
technologies for influenza vaccine manufacture, including cell-culture
based and recombinant vaccines. FDA has extensive experience in
overseeing the development and licensure of cell-culture based and
recombinant vaccines including those for prevention of other infectious
diseases, such as chicken pox, polio, rubella, and hepatitis A and B.
FDA's goal is to support a process to produce pandemic influenza
vaccine in the shortest amount of time possible and protect the largest
number of people, using a vaccine that is safe, effective and easy to
deliver. The full details of the draft Pandemic Influenza Preparedness
and Response Plan are located on the HHS website at: http://
www.dhhs.gov/nvpo/pandemicplan/annex5.pdf. Through all these efforts,
and with enhanced global surveillance by CDC and its partners, we have
the unique opportunity to effectively intervene and potentially blunt a
global pandemic, should one occur.
conclusion
HHS has proposed spending of $439 million Department-wide on
influenza related activities in the FY 2006 President's Budget. This
amount is an increase of $397 million over the FY 2001 level of $42
million, and represents the Administration's commitment to addressing
this important public health concern.
Although we may never completely prevent influenza outbreaks, we
can greatly decrease our vulnerability and provide protection against
influenza with a robust vaccine supply supplemented by effective
antivirals. FDA recognizes the need to continue to work with multiple
partners, including manufacturers, to increase supply and to support
progress toward more modern, dependable methods of production. All of
the steps we have discussed will not only help protect Americans from
flu every year but will help prepare us for future influenza seasons or
in the event that a pandemic strikes. We welcome the opportunity to
work with Congress to accomplish these important public health goals.
Once again, thank you for inviting me to testify on this very
important issue.
I am happy to respond to your questions.
Mr. Whitfield. Thank you very much for your testimony.
I will start the questioning period here.
First of all, we are dealing with a very complex issue,
when you consider the limited capacity, because I guess we only
have two or three manufacturers that are licensed to sell in
the U.S., the availability of embryonated eggs is limited, the
yield of the influenza virus from each egg, and trying to
determine the best guess of the three strains that should be
intermixed to meet the needs for the following year.
I would like to ask you initially, you each represent three
different departments in HHS. So, as you plan--could you
explain to me briefly how you interact with each other? And is
there a lead agency that, if something goes wrong, that the
Secretary of HHS could come to this agency and say, I am
holding you responsible because you are the lead agency in this
projection? Could any of you--would each of you address the
interrelationship between your departments on this issue?
Ms. Gerberding. I think it would be fair to say that,
collectively, HHS is accountable for this problem, but we each
have specific responsibilities.
From a CDC perspective, it is our responsibility to
identify strains that are emerging in this year's flu season at
the end of the season that would best predict the vaccine
strains that should be included in the following season. So we
have the responsibility for getting those isolates, for
characterizing them, for developing the seed virus that can be
used for vaccine, and then getting that to the FDA and to the
manufacturers in time for them to work on getting the
production started.
Mr. Whitfield. So you simply identify the strains and
provide the seed virus?
Ms. Gerberding. Correct.
Mr. Whitfield. And then the vaccine policy?
Mr. Gellin. The National Vaccine Program Office, as I
mentioned, was established in 1988 to do exactly as you
suggested, was to keep the arms and legs of the Department of
Health and Human Services going in the same direction on
vaccine and immunization issues. I am in the Secretary's
Office, and it is my job to keep everybody connected on this,
recognizing that there are different missions of the different
agencies of the Department. Missing from this table is NIH, who
has another piece of this, and their research and development
piece plays into this as well as broader issues about the
future of influenza vaccine.
Mr. Whitfield. Then FDA, I am assuming it is your
responsibility to make sure that the product is safe.
Mr. Goodman. Yes. Our primary responsibility is to meet the
expectation of you and the American people that it is safe and
effective and consistently and properly manufactured.
I will say, on flu vaccine, we go a good bit beyond that,
as Bruce mentioned, in terms of providing strains from our
laboratories, providing the reagents to the manufacturers to
help them in manufacturing. Also, in the recent year, in
response to this public health problem, trying to do what we
can to facilitate additional people entering the market.
Mr. Whitfield. Now, last year when Chiron had their problem
and we lost all of their dosages of vaccine, I understand that
there was some constraints on obtaining information from the
MHRA. Could someone explain to me specifically what the problem
was?
Mr. Goodman. Well, MHRA viewed that under their laws for
their regulatory body they could not inform anyone of their
impending regulatory action until they took that action. So in
fact they told us subsequently that they did not make the
decision to suspend Chiron's license until October 4, the day
before; and then all the rest is history. But they said
subsequently that they felt like they could not inform us or
any other regulatory body, WHO or others, until they had
actually taken the action. So the steps we have taken are
executing a high-level information-sharing agreement between
MHRA and the FDA.
I will say we recognize that, if this problem occurred in
vaccines, it could occur in other areas. So this is a rather
global agreement between the agencies; and it has already been
used, for example, by our drug center for sharing information
about drug safety.
Mr. Whitfield. So, prior to October 5, FDA had no idea that
there was a problem at Chiron?
Mr. Goodman. Oh, no, we knew there was a problem at Chiron.
But the issue is that we did not know--of course, as I said,
MHRA said they didn't make a decision to suspend the license
until October 4. But we did not know of that decision or that
that was on the map. We were working and receiving information
about their contamination problem and their interpretation of
that.
Mr. Whitfield. Recognizing that there is a multitude of new
sources in the U.S., there was quite a bit of confusion among
the public last year as a result of this shortage. I would like
for each of you to give your views on the way in which the
media or your Department handled communications to the public
concerning the Chiron situation and whether you see any room
for improvement in the way it was handled last year.
Ms. Gerberding. I certainly think there is room for
improvement. The challenge that we faced was starting out the
flu season expecting to have the most-ever vaccine. So, in
order to use it, we worked real hard to encourage the broadest
number of people to seek vaccination, and that is what they
were doing until October 5 when suddenly we had to backtrack
and start delivering a very different message about only the
highest-risked people getting vaccinated first.
Every year, whether we have an ample supply or not, we have
a terrible time getting people to get vaccinated after
Christmas; and we typically plan for a late season push. This
year, flu actually peaked in late February. There was time for
people in many communities to get vaccinated in January, and
yet we simply could not get that done in many communities.
So what we are doing now is working on the science of
communication, working with people trying to understand what do
they think, what are they worried about, what would help, how
can we be more effective in engaging clinicians, how can we be
more responsive to their needs and be able to get them vaccine
faster, all of the things that would help us communicate not
just to the public but also to the clinicians and the suppliers
of vaccines that have to make decisions in conjunction with
their health agencies.
Mr. Whitfield. Do either of you have any comment on this
communication issue?
Mr. Gellin. I only want to add it is further complicated by
the avian flu or pandemic flu, because we want to make sure
that people have an understanding of each of them. At the same
time, it is hard for people to often sort those out. I think
there is special communications, particularly given the
reporting on the avian flu and the concern that we all have
about it.
Mr. Whitfield. Let me ask you, what manufacturers do you
expect to produce flu vaccine for this year?
Mr. Gellin. Well, the same three that are licensed we
expect will be able to produce vaccine. Dr. Goodman has
provided insight into his recent visit to the MHRA and Chiron
facility.
In addition, I think that part of the lesson we learned
from last year is that other manufacturers are interested in
the influenza market in the United States. GSK particularly is
seemingly the farthest along, and there is a hope that the data
that has been assembled will allow them to get a license for a
vaccine for this coming year.
Mr. Whitfield. But we do expect that Chiron will be on
line, correct?
Mr. Goodman. Well, I should be clear there. You know, as I
said in my statement, I think it is too soon to tell. What I
did testify to is I think they've put into place and made
substantial progress in a very aggressive, comprehensive
remediation plan that deals with their manufacturing and
quality control issues. So what we are seeing is a lot of
change, a lot of change in the right direction.
But, also, as I mentioned, the rubber has to meet the road.
They are going to have to go soon into their full-scale
manufacturing, and then we are going to go in there, and our
inspectors and scientists will do their job and evaluate
whether the remediations they have put into place have been
effective. So I think things are in a positive direction, but
it is too soon to tell. So we do need to be prepared for all
possible contingencies.
Mr. Whitfield. One other comment on this communication. I
know within a week of the October 5 announcement about Chiron,
there are around 12 different agencies within HHS that do have
some responsibility for the flu policy, and within a week no
fewer than five agencies, including the Secretary, weighed in
through the press on the topic of the flu vaccine supply. And
with those five different messages coming, there was confusion
out there, and we are concerned the public might not know
really who to listen to. It would seem it would make some sense
if possible to try to coordinate these agencies on press
releases in the future. I am assuming you all would not
disagree with that.
Mr. Goodman. I agree. I think I did see--just having been
there when a lot of this was happening, I am not questioning
whether some of that happened, but I do know that among those
sitting at the table, for example, there was quite a bit of
coordination under very tight timelines and challenging
circumstances. But I think you have a very important point, and
Bruce and Julie are really the lead on this. We should
coordinate our communication as well as we can.
Mr. Whitfield. My time has expired. I recognize Mr. Stupak.
Mr. Stupak. Thank you, Mr. Chairman.
In listening to the answers and the one question the
chairman asked about how you all do parts of it to get ready
for the flu vaccine, it seems like you try to identify the
strain you expect, you provide the eggs, or at least the seeds
for it, and really the impression I got, and correct me if I am
wrong, then when you tell the manufacturers, here is what we
need, they just manufacture it, right? There is a lot of
preparatory work done by you all beforehand, right?
Mr. Goodman. The only thing I would add, sir, is that they
then take the seed strains that we provide them, and they have
to see how that performs under real-scale manufacturing
conditions.
In certain years, even when everything goes well, we might
have a strain that just doesn't grow that well. So they sort of
take these tools, but then they are the experts at
industrializing it and producing the vaccine.
Mr. Stupak. You give them the seeds, but they are the so-
called production experts?
Mr. Goodman. Right.
Mr. Stupak. Okay. What does an average price per dose of
the flu vaccine cost? Does anyone know? You tell us it is going
up 17 percent next year.
Ms. Gerberding. The average price of the flu vaccine
depends on whether it is purchased by the government for
government use or in the private sector. It has continued to
evolve over time, and it varies depending on the product. We
can get you the historical price list over time.
Mr. Stupak. Do you expect the government's pricing to go up
17 percent?
Ms. Gerberding. I think that those contracts are under
negotiation right now, so I am not sure we know exactly what
the price is going to be.
Mr. Stupak. Here is the part that bothers me, and, Dr.
Gellin, looking at your testimony on page 8, you talk about
that HHS received $50 million in fiscal year 2004, $99 million
in 2005, and 2006 includes an additional $120 million. If we
are spending all this money to strengthen it and make it more
available and accessible to people, why is it going up? That is
just my quick math here. That is a couple hundred million
dollars in less than 2 years. Why would the price suddenly go
up?
Mr. Gellin. Let me clarify. Those expenditures are
specifically directed for pandemic influenza preparedness, to
get around the vulnerability.
Mr. Stupak. You are still going to need a flu vaccine,
right, and you prepare for both each year.
Mr. Gellin. Except what we are really concerned with it is
the capacity, the global manufacturing capacity. The global
capacity for influenza vaccine is only 300 million doses a
year, and therefore, among the things we are trying to do are
to make investments and to provide incentives for manufacturers
to go down roads that they might not otherwise go down.
Mr. Stupak. If you make those investments and provide
incentives for manufacturers to get into business, it should
actually stabilize or lower the price for vaccine, shouldn't
it?
Mr. Gellin. I can't speak to the pricing, but I can speak
to the fact that what we are asking them to do is a broad R&D
program and investment in facilities, ultimately so that there
is production in the United States, because we are concerned
about that. That is a long-range strategy.
Mr. Stupak. With the investment of all this money, we are
really in no different position than we were last year.
Mr. Gellin. The investments are for our future investments
in pandemic preparedness for vaccines that are promising, but
aren't there yet. We are trying to move them along faster.
Mr. Stupak. But we are in no better position than we were
last year. In fact, we are in worse shape now than last year.
Last year at least we had three licensed, until October 5, and
then we dropped the two, and the status of it now is we have
two licensed, and Chiron hopefully will be relicensed to
produce flu vaccine, right? So what has changed since last
year, other than our suppliers have gone down by one?
Mr. Gellin. Again, let me just clarify these expenditures
are long-term investments and not responding to last year.
Mr. Stupak. My final question was we are actually in worse
shape than last year, because last year at this time we had
three suppliers. Right now we have got two and one suspended.
So if you look at it, we actually have less suppliers or
manufacturers of flu vaccine than we did at this time last
year, correct?
Mr. Gellin. Dr. Goodman has commented about the remediation
program of Chiron. I think the other lesson we learned from
last year is that there are additional manufacturers interested
in the market. GSK is an example of that.
Mr. Stupak. Where is that? GSK hasn't even applied for a
license yet, right?
Mr. Gellin. I will let Dr. Goodman address that.
Mr. Goodman. I understand your concern, but they are
actually engaged in a very active development program, and they
have stated publicly that they plan to submit a license
application to FDA in the very near future, and in time, that
if the data are good in there, and we review it and approve it,
that they would be able to bring vaccine for this year. So I do
think that is at least on track.
Another point----
Mr. Stupak. But it is not a manufacturing license. And when
is the drop-dead date that Glaxo can get their license and
still be ready by the flu season this year?
Mr. Goodman. One of the pieces that is relevant to that to
share with you that is good news there is they are a global
manufacturer. They are engaged in producing vaccine and are
licensed. So they are going to go ahead and produce vaccine no
matter what. So the issue is----
Mr. Stupak. Flu vaccine no matter what. But that is for
Europe. They have to be licensed to bring that flu vaccine to
the United States, and they haven't even applied for a license
yet.
What is the last possible date they could apply for a
license and be ready for this flu season here in the United
States?
Mr. Goodman. I think they could be licensed by us at any
time before they distributed the vaccine, and if they are
licensed, that vaccine could be distributed here. Then, as I
said, as far as we know, they are on track for their plan of
submitting an application to us very soon.
Mr. Stupak. So if they manufacture 10 million doses, that
doesn't necessarily mean they will be licensed and used here in
the United States?
Mr. Goodman. No, if they don't meet our safety
effectiveness standards or are unable to submit their
application.
Mr. Stupak. So what is the date when they have to meet your
manufacturing standards and be licensed so they are ready to go
by this flu season? Because, doctors, there is no difference;
in fact, we are in worse shape now than we were last year. So
what is the drop-dead date?
Mr. Goodman. As I said, vaccine is typically delivered in
the fall, so my view would be as long as they succeed in their
license application before the fall, they could bring vaccine
to the U.S. market.
Mr. Stupak. I heard a couple of ifs there. The part
bothering me is going back to the statement found in Dr.
Gellin's statement, it says, ``Companies need to plan the
amount of vaccine they will produce well in advance of the
influenza season so they can secure the needed egg supply in
which vaccine viruses are grown. Production of annual influenza
vaccines, which contain three different influenza viruses,
takes about 6 to 9 months.''
If the flu season is October 5, since that seems to be the
date we all got in trouble last year, that is like 5 months
from now. So if you are 6 to 9 months, we are lessening that
window period.
Mr. Goodman. I understand your concern. Again, to be
helpful in addressing it, what I could point out is they are
producing that vaccine. So their plan is to produce it
irregardless of our license or decision. They are producing it
at risk.
Mr. Stupak. You are right, because they can produce all
they want, but if it is not licensed in this country, it
couldn't do us any good. GlaxoSmithKline can do 100 million
doses, but if it is not licensed for use in this country, it
does us, the American people, no good, correct?
Mr. Goodman. You are correct.
Mr. Stupak. Let me ask you this: Exactly what would an
expeditious licensure by the FDA be if Glaxo decided to enter
the market, 6 weeks, 3 months, 6 months? What is expeditious?
Mr. Goodman. You mean the time from when we receive their
application to the time they approve it or don't approve it? I
think that what I can say about that is, again, we have made a
commitment that if we can get a high-quality application with
the data in it that supports the safety and effectiveness of
the vaccine, that we would be able to review that, and, if the
data support approval, approve it before the flu season.
Mr. Stupak. How long will it take, 3 months to approve it,
2 months to approve it?
Mr. Goodman. I think it depends on whether--you know, we
are doing a scientific job there. It depends on what the data
show, whether there are any concerns raised and we have to ask
the company additional questions, et cetera. There is some
positive information there in terms of they were one of the
firms that we interacted with and inspected back in October-
November to try to get IND vaccines. So they are not starting
from a zero knowledge base.
Mr. Stupak. The answer would depend upon the quality of
their application, right?
Mr. Goodman. The quality of the application.
Mr. Stupak. Scientific data with it?
Mr. Goodman. Absolutely.
Mr. Stupak. Then do you have to do a full-scale
investigation as to their manufacturing safety?
Mr. Goodman. We were there last year, but we would again
go, and the American people expect us to review their
manufacturing. We would do that expeditiously also.
So you are correct, there are ifs there. I wouldn't want to
promise something that basically is a scientific process.
Mr. Stupak. Sure. I am just trying to get some kind of
timeframe here.
Dr. Gellin, the committee staff talked to the British
counterparts. They mentioned that Britain did not rely on just
one or two manufacturers for their influenza vaccine like the
U.S. Does. That was a problem we had last year, but the
situation again is exactly the same.
Sanofi will be the supplier of at least 75 percent of our
flu supply if we get the 80 million doses normally consumed,
and Chiron will supply most of the remainder. It looks like the
situation will not change in the near future. So what are you
doing at the policy level to sign up new suppliers, or are we
still at the mercy of the market?
Mr. Gellin. Our goal, I think, beginning last year was to
try to have a better understanding of the market and
particularly what was going to be the incentives for new
companies to come into this market.
Mr. Stupak. So what are those incentives?
Mr. Gellin. As Dr. Gerberding mentioned, the incentives
there is increased demand, there is increased interest in the
product, and the price has gone up substantially to make it a
more interesting market for them.
Mr. Whitfield. The gentleman's time has expired.
At this time I recognize the chairman of the full committee
for his question period.
Chairman Barton. Thank you.
How many flu shots did we end up giving to American
citizens this flu season?
Ms. Gerberding. We gave approximately 57 million.
Chairman Barton. Fifty-seven million. As it turned out,
everybody who really needed one got one; isn't that right? At
the time we thought there were going to be a lot of people that
wanted them that couldn't have them?
Ms. Gerberding. Let me distinguish need and want. From our
perspective as doctors and public health officials, we believe
that about 185 million people need a flu shot, because the
science says they would have a serious benefit from it.
In terms of the number of people who want flu shots, that
seems to be influenced by concerns about scarcity and concerns
about the severity of the season. About this year 57 million
people wanted a shot.
Chairman Barton. What is the most inoculations we have ever
given?
Ms. Gerberding. Eighty-three million in the year that we
had a supply of about 87 million doses.
Chairman Barton. When was the 83 million?
Ms. Gerberding. That was in 2002-2003 flu season. I should
add that in every single flu season, regardless of how much we
have, we always end up wasting somewhere between 4 to 12
million doses of vaccine that manufacturers produce but people
didn't want.
Chairman Barton. Given everything that you all have done in
the last year to prepare for next year, and you are continuing
to do, what is the most probable number of flu shot vaccination
doses that are going to be available in the coming flu season?
Ms. Gerberding. We have to plan for all three scenarios. We
have to plan for the scenario where we don't get these licensed
products here and available for us, so we will have about the
same amount of vaccine that we had last year; we have to plan
for the scenario where we might have the most ever, if
everybody produces and brings their vaccine to market here;
and, of course, as a backup, we have to plan for sort of the
worst-case scenario, that something goes awry with our primary
suppliers.
Chairman Barton. Give me three answers then. Worst case.
What is the minimum number?
Ms. Gerberding. Well, the worst-case scenario, I would say,
is we would have somewhere around 53 million doses.
Chairman Barton. So the worst case is a little bit less
than last year. What is the best case?
Ms. Gerberding. Probably around 98 million doses.
Chairman Barton. Ninety-eight million, which would be more
than we ever used.
Ms. Gerberding. Correct.
Chairman Barton. What is the most probable case or the
midterm case?
Ms. Gerberding. I can tell you what the middle-range
scenario is. That is 75 to 83 million doses.
Chairman Barton. Unless we have a worst-case outcome, this
committee can be reasonably confident that every American next
year that really needs a flu shot is going to be able to obtain
one? Is that a fair statement?
Ms. Gerberding. That is not quite true. Again, it is the
difference between needing and Americans who want a shot.
Chairman Barton. The most we have ever given was 83
million. Last year we gave 53 million. You just said the most
probable case is in the 70 to 80 million range. So probably
everybody on this panel up here needs a flu shot. I am not
going to ask for a show of hands, but I didn't get one last
year, because if I had, I probably would have been accused of
favoritism. Since I have never had a flu shot, I figured I
could go 1 more year without getting one.
Ms. Gerberding. Maybe you would like to talk to me later.
Chairman Barton. If you talk about need, I am probably at
the top of the list of need.
What we don't want to do is go through another year like
last year where at the beginning of the flu season there are
all these press stories that there is a shortage, and that you
kind of have panic vaccination mode. And then in the middle of
the flu season it turns out we have got more doses available,
and that is to the credit of you three, that you went out, and
the Secretary of HHS went out, and we talked to our friends
overseas, did a lot of good work and got more doses. So it
turned out to be not as bad as we had thought. As people who
get elected, we don't want to go through this feast and famine
in the middle of a flu season.
So this subcommittee, the reason of this hearing is to find
out what you are doing different from last year, what the
prognosis is for next year, and whether we need to really,
really, really do aggressive oversight. If your midcase
estimate is right, I am going to assume that things are in
reasonably good shape, and we need to monitor it and touch base
with you, but most Americans are going to be able to get a flu
shot next year. If I am wrong in that assessment, this is the
time to tell the subcommittee that, and if we need to do
something legislatively or in the appropriations process or
encourage some sort of negotiations overseas, now is the time
to do it.
Ms. Gerberding. Let me emphasize two things. One is that
the highest priority is to get those vulnerable people
vaccinated. Right now, even under the worst-case scenario, we
would be able to come close to having the amount of vaccine we
did this year, and we will know that at the beginning of the
year. So we do feel like our most vulnerable people will have a
pretty good chance of getting a vaccine.
Chairman Barton. Do the other two witnesses share that
assessment?
Okay.
My last question: If I need to call one person and get the
straight answer on some of these issues, and we got three of
you, but my assumption is that one person would be the
Secretary of HHS, Governor Levitt. Is that the person I should
call, or is there somebody else?
Ms. Gerberding. I don't want to speak for the Secretary. He
obviously is very engaged and very up to speed on this. I am
sure if you called him, he would either give you the straight
answer immediately or send you to one of us.
Chairman Barton. Who would you call?
Ms. Gerberding. I would probably call him, too.
Chairman Barton. Okay. What about the other two? Is that
who you would call?
Mr. Gellin. Well, he calls me pretty often about these same
issues.
Chairman Barton. He calls me, too.
Mr. Gellin. That is where it all gets put together.
Chairman Barton. You agree with that?
Mr. Goodman. I think that is appropriate.
Chairman Barton. Thank you, Mr. Chairman.
Mr. Whitfield. We have a vote on the floor. We still have
12 minutes to go. I am going to recognize Ms. DeGette.
Ms. DeGette. Thank you so much, Mr. Chairman. I just have a
few questions.
I am wondering, we have been talking about GlaxoSmithKline
entering the market, and they are not licensed, and are all
hoping they will be licensed. What backup plan do you have in
place if they are unable to provide the expected 8 to 10
million doses?
Ms. Gerberding. There are two backup plans. One is the one
I mentioned about the scenario planning, so we are planning as
if we couldn't get that vaccine, and that is why we are going
to start focusing vaccination early in the season on the high-
risk people and letting other people know that if everything
goes right and we have the vaccine supply we think we are going
to have, we will make clinics available for other people later
in the season.
The second backup is what we refer to as the insurance
plan, and that is we have in the proposed budget $30 million so
we can buy monoviral bulk vaccine from any one of the
manufacturers that would be available to us, either as a
licensed product or as an investigational product, that can be
then brought into dosage forms if necessary if everything else
fails. It is not the ideal backup, but it is a way for us to
expand our market even further beyond Glaxo, beyond Chiron,
into anybody in the world who manufactures flu vaccine.
Ms. DeGette. Why is that not ideal?
Ms. Gerberding. Because it is investigational, and it means
we would have to get consent from people to be able to use it.
Ms. DeGette. It also seems like it could make people really
nervous and even more upset than they are about the real
liability.
Ms. Gerberding. It is insurance. It is the backup to the
worst-case scenario.
Ms. DeGette. Well, let me ask you this: I am still
concerned that pharmaceutical companies, as I mentioned in my
opening statement, are not motivated to manufacture vaccines,
and I am wondering, maybe from you, Dr. Goodman, what we could
do to improve this situation?
Mr. Goodman. Well, I think it is an important question, and
it is something we need to pay a lot of attention to. I think
recognizing in pricing and purchasing and in our health care
system the public health value of some of these interventions
can be very helpful.
Ms. DeGette. I don't know what that means. Does that mean
we should let them charge higher prices or what?
Mr. Goodman. Well, you know, we at FDA don't get into the
pricing issue at FDA, but what I will say is in terms of the
public health benefit, if we look at the prices charged, if we
look at prices that are paid for various things in terms of
public health benefit, vaccines are often very cost-effective.
One comment I was going to make, although we have
identified serious problems and fragility in the vaccine
infrastructure, and you are very concerned about that, there
are some positive developments, too. People are making new
vaccines against human papilloma virus, which causes human
cervical cancer. We have had the first ``blockbuster'' vaccine,
pneumococcal vaccine against pneumonia in children, which has
huge sales every year. So a number of companies are actively
engaged in developing new vaccines in the vaccine market.
Ms. DeGette. But if the FDA's job isn't to get involved in
figuring out the public good versus the pricing, then it seems
like we are acting at odds against the public interest, because
if prices of these vaccines go up, fewer people will have them,
and then when we have our pandemic or whatever, it is going to
be worse. It seems to me there have to be other ways to
incentivize the economical and widespread manufacture of
vaccines from a public interest standpoint. This is not about
can the pharmaceutical companies make a profit on vaccines, it
seems to me.
Mr. Goodman. No, I agree that is an important area. For
example, in flu vaccine, I know CMS in recent years has, to
some degree, done this by its reimbursement policies, and that
has affected flu vaccine use.
Ms. DeGette. Is that something we should continue to look
at, that policy, Dr. Gellin?
Mr. Gellin. Absolutely. I don't have the numbers in front
of me, but that has gone up dramatically as far as
reimbursement costs of those. I think we can get into that a
little bit here, but maybe we can have a separate opportunity
to talk about the vaccine industry at large.
I think, as I mentioned, the flu vaccine is somewhat of a
special case, but I think some of the things going on and the
awareness that we have of a number of companies that
manufacture influenza vaccine and are interested in the U.S.
market gives us promise that some of those pieces will attract
additional manufacturers to the marketplace.
Ms. DeGette. Mr. Chairman, I think this would be a ripe
issue for a future hearing.
Ms. Gerberding. May I just add that the flu vaccine is
actually the lowest priced of any of the vaccines that we
routinely recommend.
Ms. DeGette. As it probably should be.
Ms. Gerberding. We have to say why wouldn't a manufacturer
be in the market that should be selling 185 million doses? One
issue is that they are not confident they can get a fair price.
Another issue is it is tremendously risky.
One of the things that I think Dr. Gellin referred to
earlier that I don't want to be lost on the committee is the
fact that the Department has provided hundreds of millions of
dollars to the manufacturers to say, please modernize your
vaccine production. Let's get out of eggs into cells. Let's
move forward and build some plants. Let's get the show on the
road here. So they have been providing these incentives to move
this forward.
Ms. DeGette. What is happening with that process?
Ms. Gerberding. Those contracts, the most recent round was
just announced, I think, last week.
Ms. DeGette. Is it working?
Ms. Gerberding. Science takes time, so it will be a while
before the actual research and development gets to the point
where we have a product, and not before flu season this fall, I
am absolutely certain of that. But it is an important step. For
the government to incentivize this kind of R&D in a very
targeted way, I think, is the appropriate step, and I am glad
we are able to do that.
Ms. DeGette. I just have one more question. Dr. Gerberding,
you were talking about this throughout the afternoon. Part of
the problem last year, and it is going to be a problem if we
have limited supplies again in the fall, is this whole issue of
the people who should get the vaccine don't get it. This
happened last year where we had a shortage, so a lot of the
target population didn't realize they were the target
population, they didn't get it, and then as time goes by, they
just sort of forget.
I am wondering if you can supplement your answers by
providing for the record some kind of plan for how you are
going to reverse that thinking. Just saying you want to reverse
it, you know, that is not going to solve the problem next year.
Ms. Gerberding. We will be happy to provide that.
Ms. DeGette. Thank you very much, Mr. Chairman.
Mr. Whitfield. We have 5 minutes left to go cast a vote,
and then we will have one more vote, which we will vote on
immediately. So we are going to recess this hearing. We will be
back here in 10 to 15 minutes. We will recess for 10 to 15
minutes.
[Brief recess.]
Mr. Whitfield. We will reconvene the hearing. I will
recognize the gentleman from Texas for his questions.
Mr. Burgess. Thank you, Mr. Chairman.
If I might just back up a little bit. I know Mr. Stupak
asked the question about the cost per influenza vaccine, and I
don't know that I actually heard the number. Can you tell me
that, Dr. Goodman or Dr. Gerberding?
Ms. Gerberding. What I have is the catalogue price. So for
a multidose vial of the Sanofi Pasteur vaccine in 2005, the
catalog price is $9.95. For the thimerosal-free syringe, a half
millimeter is $13.25. The MedImmune single dose is $24.50.
Mr. Burgess. Okay. I know you went through, Dr. Gerberding,
a scenario of the various numbers of the flu vaccine that were
used when the chairman asked the question, but what is the
greatest number of doses that the market can handle in a given
year? Is it that upper figure, that 83 million doses are the
highest that have ever been given?
Ms. Gerberding. The most doses that have ever been
purchased was the 83.1 million.
Mr. Burgess. Is that the upper limit for the market?
Ms. Gerberding. No, I don't think so. That number was used
in a year when we had not yet made the recommendation about
immunizing infants, and the number of infants to be included is
approximately 6.5 million more. If we got 50 percent of those,
that would increase that.
We are also working harder and harder on some of our
hardest-to-reach risk groups, like children with other medical
conditions that makes them especially vulnerable to influenza,
and all the time more data are being scrutinized by our
scientists and our advisers that might expand the market
indications even further as we learn.
For example, it is possible in the future we may learn for
all children there is an advantage to immunization. It may be
less days missed from school or less days missed from work for
their parents. But those are the kinds of questions emerging in
our research portfolio on an ongoing basis. So it is not a
static situation, it will evolve over time.
Mr. Burgess. Very well. Since you brought it up, I wasn't
going to say the word thimerosal, but you brought it up. Will
the cost for that thimerosal-free syringe, are we reimbursing
the manufacturer at a rate where they can make a profit on
that?
Ms. Gerberding. I really can't speculate. I would assume
so, because they wouldn't do it if they didn't find it to be a
profitable enterprise. But I would have to defer to their
economists to answer that question.
Mr. Burgess. But there aren't that many of them doing it.
Now, with thimerosal-free vaccine, is that pretty much what
everyone has gone to?
Ms. Gerberding. The Department and the CDC have recommended
for several years now that all vaccines for children be free of
thimerosal as a preservative, and manufacturers have done that
with all other vaccines.
The current flu vaccine manufacturers are converting over
to be completely thimerosal preservative-free, and I believe
the GlaxoSmithKline product that is in the pipeline is being
formulated that way to start out with. So in a brief period of
time, I believe the manufacturers will be utilizing vaccines
that do not contain thimerosal as a preservative.
Mr. Burgess. For all of us, for adults and children alike?
Ms. Gerberding. The issue is if you are using a vial of
vaccine that has more than one dose in it, it needs to have a
preservative.
Mr. Burgess. Very well. Now, last fall when I wasn't on
this committee, but I was on the Government Reform Committee,
and you testified in front of that committee, we talked a
little bit about the ability to dilute the vaccine that was
available. Were there any studies undertaken last fall with
diluting the available flu vaccine stocks to try to extend them
further?
Mr. Gellin. I am not certain. I think I need to get back to
you. The Defense Department may have participated in a study
like that. We will get the facts back to you.
Mr. Burgess. So at this point no data is available. If we
come up against another crisis, Mr. Stupak is concerned that
nothing has changed from last year. But one thing that might
have changed is we might have some data on what happens if we
dilute the vaccine in the more healthy of the population and
extend our vaccination range that way.
Mr. Gellin. Recognizing that we would have to then apply--
if it was last year's vaccine, it would have to make the link
between next year's vaccine as well. But I think that is the
case.
Mr. Burgess. Dr. Goodman, when we heard the testimony last
year on the Government Reform Committee, the contaminating
agent, I was told, was a bacteria called Serratia, which is not
a very pathogenic organization and one that likes to live in
water baths and so forth in labs. Do you know where the
Serratia came from that contaminated the vaccine last year?
Mr. Goodman. There is not a definitive answer to that
question. It was clearly an environmental problem in the
facility. I believe that we feel it was introduced in the
environment most likely at steps involved in not the initial
growth of the vaccine, but the formulation, and it points out
the importance of environmental control in this kind of
facility.
Mr. Burgess. Are there any procedural changes that have
been undertaken to avoid this happening again, or is that all
depending upon getting away from the egg-based system to a
cell-based system?
Mr. Goodman. No, there are quite a number of steps in terms
of the manufacturing process that in this case Chiron has
improved to reduce the risk of that kind of problem. These
problems--I should state you are correct in asking about egg-
based vaccines in general. These kind of problems, the egg-
based production is more prone to them. But what is needed then
is the testing and quality system in place to, if problems
occur, promptly identify, isolate it, and assure it doesn't
affect your general production.
Again, quite a number of the steps that were proposed in
their remediation address exactly this kind of issue; keeping
the clean areas clean, assuring prompt and proper action when
problems are detected, and handling the process in a way that
is as aseptic as possible.
Mr. Burgess. When you say when problems are identified,
taking prompt action, what type of action? Would that be to
sequester that part of the lab or that batch of vaccination?
Mr. Goodman. There could be many different kinds of
problems detected, and the responses might be different. Let's
say, for example, vaccine manufacturers do frequently and
carefully monitor the environment in which manufacturing is
performed and look for excursions that suggest problems with
control of the environment. When you find those, it is
important to act quickly, investigate the cause and prevent
further problems. That would be one example; then certainly if
you note this in a product, very promptly investigating and
trying to understand, by looking at safe samples, looking at
the process that occurred, where did that occur, and do we
understand that that is isolated and that the other lots are
acceptable.
Mr. Burgess. Again, I would just point out, that might be
one other thing that would fall into the broad category of what
has changed since last year when we found we didn't have enough
vaccination.
Let me just state for the record that I did not take a flu
vaccine last year. The only people that were concerned about it
were CNN, but they did seem to be very interested if I did have
a vaccination. I didn't. If it will help you, Dr. Gerberding, I
will take one this year. But you tell me if it is okay. I will
wait for your word.
In the brief time I have left, I will ask Dr. Gerberding,
you have described several scenarios for us, best-case, worst-
case scenario. Do you have in mind, and I don't mean to get too
far into the science fiction aspect, but do you have an idea of
what the pandemic scenario would look like? What would we see
as Members of Congress, what sort of reports would be coming to
us from the field, what would you all be seeing before we were
aware of it, what would you be doing and how would you make us
aware that there was, in fact, a problem creeping up on us of
that magnitude?
Ms. Gerberding. Thank you. As you know, we are very
concerned about the situation with avian flu in Asia. That is a
good example to use the what if story from.
The first thing we would expect if this new pandemic
unfolded the way the previous ones did, we would begin to see
more clusters of flu in people and evidence that those clusters
were expanding in time. In other words, one person is infecting
their neighbor and the next person. So we would see an expanded
timeframe for the clustering.
Often as flu evolves, it doesn't just make a sudden jump to
become very transmissible in people; it gradually gets there
over a period of weeks or months. So those clusters are very
important sentinels of impending transition to a virus that
could be more easily transmitted and potentially cause a
pandemic.
The main reason we are worried about pandemic with this
virus is because no human beings around the world have ever
seen it. None of us have preexisting immunity to it. So that is
where we are so especially concerned about this avian flu.
What we would do is identify the clustering and also have
the viruses themselves so that we would be able to characterize
them in our laboratories or in the World Health Organization
collaborating laboratories and try to make a connection between
what is going on in the people and what is going on in the
virus. We would also take those viruses as they emerged and
work on making a seed virus very quickly so we could put it
into the manufacturing processes that we have for flu virus.
One scenario is that we would convert from making the
regular seasonal flu virus, which, incidentally, has three
virus strains in every vaccine, into a vaccine that had only
the pandemic strain in it. So instead of having a global
capacity to make 300 million doses, we would be able to at
least get 900 million doses out of it. So we would try to
expand our supply by making a single-strain vaccine. But the
timing to do that, as you know, is many months, so in the
interim, what we would concentrate on is, first of all,
containing the outbreak at the source through quarantine,
isolation and use of our antiviral drug Oseltamivir.
In addition, if we had a limited supply, we which we do now
of this particular pandemic vaccine, we would use that to help
support immunization in the people closest to the exposed cases
and try to buy some time while we were scaling up our vaccine
supply.
But if you think about SARS where we had no drugs and no
vaccine, the world was able to contain that outbreak by using
old-fashioned methods of isolation and quarantine. The one
difference is, of course, that flu is probably transmitted much
more efficiently than SARS was, in retrospect.
So it would be a very big challenge, and that is exactly
why we are spending so much time every day at the Department
preparing all the steps in the process, the detection steps,
the stockpiling of the drugs to treat the flu, the development
on a fast track of the manufacturing processes for an avian
vaccine that would allow us to scale up and reduce the time to
produce it by a few months under emergency conditions.
All of that has to include not just the government at the
Federal level, but communities across America as well as the
globe.
Mr. Burgess. Mr. Chairman, I should point out that with the
SARS situation, NIH identified that virus with gene sequencing
techniques, and within 30 days they pretty much knew the virus;
is that correct?
Ms. Gerberding. No, actually it was CDC that did that.
Mr. Burgess. Oh, was it. I am sorry. Thank you.
Mr. Whitfield. I recognize the gentleman from Washington
for his questions.
Mr. Inslee. Thank you, and thanks to the panel for waiting
for us. We appreciate that.
Dr. Goodman, I wonder if you could tell us what incentives
exist, what you are working on, if anything, both through a
commercial aspect and through regulatory aspect to really
create incentives for new entrants into the market
domestically?
Mr. Goodman. Well, we at FDA don't have financial
incentives to offer. What we can do is try to provide what I
would classify as a very rich, productive, helpful interaction
with manufacturers, and also to try to be sure that the
expectations that we put forward in terms of safety and
effectiveness and how manufacturers meet them are balanced and
get us the information we need without creating undue burdens.
So we have been very engaged in that with the flu
manufacturers.
Every year, even with the existing manufacturers, we have
extensive interactions. As you heard, we provide them with seed
viruses and reagents that are helpful to them.
In addition, the other thing we challenge ourselves to do
is say can we look at the data and say can we help them speed
the clinical development program, and that is where we came up
with the accelerated approval mechanism based on the likelihood
that good antibody levels against the virus will predict
protection. This has allowed, for example, in the case of GSK,
them to accelerate their plan by 1 to 2 years to come to
licensure.
So those are the kinds of things we can do to help make
this a faster, more economic way to market. But we can't
provide ourselves any economic incentives. The market provides
those.
Mr. Inslee. Any thoughts from the other two agencies in
that regard?
Mr. Gellin. Let me add to that. As Dr. Goodman said, there
is the market piece. It is also important to appreciate the
demand and use of influenza vaccine over time that Dr.
Gerberding has mentioned. The peak of our use has been in the
mid-80 millions, but recognizing just as briefly as maybe 10
years ago, the marketplace was far smaller than that with maybe
30 million doses as the annual allotment.
So I think a big part of it has been not only the increased
awareness by the population of protective value of the vaccine,
but the expansion and recommendations has created a bigger
marketplace overall.
Mr. Inslee. Dr. Gerberding, any thoughts?
Ms. Gerberding. I would agree that driving the demand for
the vaccine is an important and critical step actually. We do
this by science. We do the research, we find out who is going
to benefit from the vaccine, what is the benefit, what is the
cost-effectiveness of the vaccine. And as we identify that in
new populations, we make recommendations that we should be
vaccinating these people. That influences what the government
pays for; that influences what CMS reimburses for. So we can
drive forward the market, and we have done that over the past
15 years, by expanding the number of people that we recommend
in the immunization pool.
There is consideration now, though there has been no
decision on this, that the pool be expanded even further. I
mentioned the possibility that we would end up with enough
evidence to recommend universal vaccination of children, for
example, for flu every year.
I think ultimately the big payoff will be the manufacturer
who identifies a better vaccine, and by that I mean a vaccine
that we don't have to give every year, a vaccine that could be
given once or twice in life like all of our other vaccines and
really get us beyond this annual challenge that we face.
That is a matter of basic science, and that is why these
investments that the Department is making in motivating the
science, not just through the research grants that the NIH is
putting out, but also through these contracts with
manufacturers to try to develop a better vaccine, are so
critical for the mid to far term of this problem.
Mr. Inslee. Given this pandemic possibility, which is kind
of disconcerting, should we be giving thought to accelerated
FDA approval of some of these to try to inspire new entrants
into the market? I am told it is about 12 months. Is that
realistic? If so, is there anything we can do to accelerate
that?
Mr. Goodman. We are applying similar principles to the
pandemic vaccines as we are to trying to bring additional
manufacturers in for the routine vaccines. So you are
absolutely right, we see that as an issue, and we are doing
that.
In fact, with the U.S.-licensed manufacturers, we view a
new vaccine for a pandemic not as a new vaccine that would
require a new license, but as a change in strain such as we see
each year. So the data we require is very different, and we are
able to really facilitate that process.
Mr. Inslee. So what is the time span then from start to
finish?
Mr. Goodman. It is primarily related to their ability to
manufacture and then submit to us data about that strain.
Mr. Inslee. What does that end up in the real world being?
Mr. Goodman. Well, you know, typically, for example, one of
the things, as Dr. Gellin mentioned, is the Department has
funded the production of an investigational or new vaccine
against the current avian influenza strain. Because the immune
response to these viruses, one of the issues why it is a
pandemic, it is because you or I have no experience against
that virus or its relative, so we can't always predict how good
our immune response will be.
But in this case, Aventis Pasteur very quickly produced a
commercial scale lot. I actually don't want to give you a
number, but it just was within a very few months, and that is
undergoing testing. Now, in fact, I think most--a bunch of that
testing has already been completed, supported by the National
Institutes of Allergy and Infectious Disease.
So a manufacturer with a licensed existing technology and
manufacturing capacity, provided with the right virus, can very
quickly begin to produce it for the initial testing, and then
we would look at that data and be able to evaluate it.
I think the real issue here that we are also concerned
about is what is the manufacturing capacity out there to
produce the millions and millions of doses that would be needed
and the time that is needed to do that. As you have heard, it
typically takes several months to ramp up and produce enough
vaccine for the whole U.S. population.
Mr. Inslee. So I am trying to get some sense of the time in
days, months, weeks, portions of centuries, some timeframe, and
if you can break it down from the time they have some
manufacturing capacity demonstrated, from there, how long would
it take the FDA to do the evaluation to really get the
certification?
Mr. Goodman. As I said, we would not consider it a new
vaccine, so the major factor there is how long it takes them to
produce the vaccine.
Mr. Inslee. Say it takes 3 months to produce a vaccine. How
much longer?
Mr. Goodman. They would do a clinical study, for example,
to show the immunogenicity and safety of that strain. We would
probably require limited data, and they would submit that data.
They could potentially do that study, I think, as has been
done, for example, by GSK, within a matter of a couple of
months. Then they would submit that data, and we would look at
it very quickly. We do this every year.
So, again, we would not be the limiting factor there,
unless a problem with the vaccine were to occur.
Mr. Inslee. Say it takes 3 months to do the manufacturing
capacity, 2 months to do the clinical trials. How long--if you
would give me some parameters of how long it takes the FDA to
finish that? I am just looking for parameters.
Mr. Goodman. Each year we review a new strain submitted.
For example, if they change a strain in a vaccine, each year we
review that, and we typically do that within a month. This may
be more complex if there is more data.
Mr. Inslee. Okay. Could you give us any thought about the
difference between the European system and ours relative to
their experience with this? I sense there is--and maybe it is
this one difficulty we have run into--is there a different bar,
a different screen they are running through to have a different
experience, and if so, does that give us any thoughts on ours?
Mr. Goodman. Regulatory?
Mr. Inslee. Yes.
Mr. Goodman. Well, there is not one European regulatory
system, so for traditional vaccines, there are multiple
countries that can review and approve those vaccines. They may
do it similarly or differently.
For the routine strains, there are some differences. For
example, each year clinical studies and clinical information is
required by the Europeans, so in other words, they take the new
vaccine that is made each year for annual influenza production
and actually require that the manufacturers provide a small
clinical trial of that vaccine. At FDA we view them as strain
changes for licensed vaccine, and we don't require that. So,
that is one difference that each year they require clinical
data, and we don't. I would say that is a major issue.
Similar to us, they have inspections, and you can see, for
example, with Chiron, there was an independent inspection by
the EUK regulatory authority of that manufacturer, which was
located in England.
But the main difference is--I can't say there is one
systematic difference, that one country is tougher or weaker or
anything like that, but there is this one major difference,
which is that they are required to provide clinical data there
each year. We feel we have had enough experience with the
routine strain changes and the licensed manufacturers that we
are comfortable just making sure that strain is exactly what it
is supposed to be and the potency and safety of it are proper.
Mr. Inslee. Great. Thank you very much.
Mr. Whitfield. Thank you.
I recognize the gentlewoman from Tennessee for her
questions.
Mrs. Blackburn. Thank you, Mr. Chairman. I want to thank
all of you for your patience. I know it is disconcerting
sometimes as we are in and out and going for floor votes.
Director Goodman, I think I will come to you first. I had
done a little bit of reading in preparation for the hearing
today, and I found a great article, What Is Wrong with Our Flu
Vaccine Supply, and actually highlighted a few points in here.
I found it quite interesting. It seems like basically if you
were to say the underlying problem or the root of the problem
goes back to being this, and it is because of liability,
because of regulation, because of maybe some changes in public
policy through the 1990's that the U.S. has become a less
friendly environment for U.S. vaccine manufacturers. Then you
begin to look at some of the situations that arise because of
that and the liability and the different situations that exist
because of that.
With all that said, taking that as a premise, a question
that I have got, in reading this, I was looking at the
developmental strategy, the multiple developmental strategy of
when you are looking at a strain, and why is it impossible to
have a multiple strategy, a multiple developmental strategy,
for one of the vaccine formulations? And then how could we get
to the point that we have multiple developmental strategies for
the vaccines, for a specific vaccine, for a certain flu, to be
certain that--I think Dr. Gerberding mentioned earlier that
sometimes you pull a certain strain, but you don't know if that
is going to be what you end up needing or not or if it is going
to replicate itself well or not.
So, how do you get to the point that you develop those
multiple strategies?
Mr. Goodman. I want to be sure I understand your question
before I answer it. I can see two questions there. One is would
it be possible to develop a vaccine that protects against
multiple different strains? The other would be if we have
problems such as Dr. Gerberding mentioned occasionally where a
strain is circulating and we didn't predict that it would be
important, could one have prepared a vaccine against that ahead
of time?
Mrs. Blackburn. Right. Take both questions.
Mr. Goodman. The first one is really a science question. It
is something that the Department and NIH and FDA are all
supporting research on. It would be ideal to have a vaccine
that protects against multiple strains without having to every
year go out and find all those strains and grow all those
strains. So people are trying to find proteins in the vaccine,
in the virus, that might provide protection in multiple years
or against multiple strains. That kind of research is going on.
There is some evidence that there may be some advantages for
live attenuated vaccines in providing that kind of protection.
So there is a lot of work going on in that, and it is a
Holy Grail, and it would be very desirable and could even help
protect us against pandemics potentially. But the science isn't
there yet, and it has been difficult to achieve.
The other question is really again limited by the capacity
of the industry. So as manufacturing gears up, the industry,
based on CDC and WHO's surveillance data, FDA's expert
committees, tries to examine what has gone on out there in the
world and pick the strains that are likely to threaten our
population and put them in the vaccine. In general, they have
done a remarkable job at doing that, but occasionally there is
a strain that circulates in one part of the country or another
that causes a problem and isn't well covered by the vaccine.
As you said, you could deal with that by potentially, if
you saw something possibly emerging, making some vaccine
against that strain. The tradeoff there is right now the total
capacity is limited, so you would have to cut back on someone
else. So right now we are unfortunately in the situation of
people making the best educated decision and then going ahead
and producing. I don't know if Dr. Gerberding or Dr. Gellin
want to add to that.
Mrs. Blackburn. Well, I think that is probably one of the
things that is just a continuing source of frustration. And I
am sure Director Gerberding has a certain amount of that. It
seems there is a flu virus that you all, if I am understanding
that correctly--you may identify something in the spring, and
then by the fall there is another strand that you have nothing
for that is actually causing the flu, the outbreak, the
epidemic, whatever. And then is there anything that you can
begin to do, either through preparation or through science that
the CDC can do, to take some steps to forestall that?
Ms. Gerberding. The virus is very unpredictable, and it is
usually not just one virus circulating during a flu season;
there are several, usually at least three and often many more
variants than that. And so we use our experience and our
predictions based on the past early in the spring to look at
what is present at that point in time, because in most years
what is present in the spring is what is going to be present in
the fall. That doesn't always prove to be correct.
But what usually happens--and this example happened last
year where the vaccine predicted strain was a toss-up. We
didn't know if it was going to be a Fujian strain or whether it
was going to be a different strain, and we wanted to have the
best chance of coverage. Unfortunately, the Fujian strain
didn't grow very fast when we were trying to create the seed
virus. And we had to make the decision we had better go with
the one we can get a vaccine to because there is no room to
wiggle in the timing of getting these products to market.
So the vaccine that was produced that year wasn't a perfect
match for what turned out to be the dominant strain that fall.
Fortunately, there was crossover. So the strain that we did use
was a close cousin, and there was some protection afforded to
people. And that is usually what happens even if it is not a
perfect match. If it is a cousin instead of a twin, we get
reasonably good protection of the people who need it the most.
But there is right now no way to accurately predict which
one of the swarm of viruses is truly going to emerge, and
sometimes we don't get it right. What Dr. Goodman is really
describing is the fantasy that we all have, that we will find a
way to make a vaccine against some part of the flu virus that
doesn't change every year, some other molecule in the virus
that is consistently there that would be a good enough source
of protection that would allow us to just vaccinate using that,
and then it didn't matter about all these other changes that go
on and on and on. But we have no proof of that principle yet,
and, believe me, everyone would like to find such a vaccine. It
is a little bit like the AIDS vaccine, where the virus changes
so much over time, you can't pin it down and find something
that will uniformly protect against all strains.
Mrs. Blackburn. And if I am understanding correct, ma'am,
it is basically what is happening with this is that you
mentioned the wiggle room, and you have very little time to
move. You do a lot of work on faith, basically, and informed
science and then a little bit of faith. And then you move
forward into production, but you don't have a lot of time for
testing.
Ms. Gerberding. That is exactly right. If we pick the
strain, let us say we find it in February or March, we have to
make the seed for the vaccine from that in a matter of weeks,
get that off to the FDA and the manufacturers who have to put
it into production mode. And it is not just about popping it
into some eggs. It actually takes time to grow in the eggs. It
has to be harvested; it has to be processed so that all of the
potential contamination from the eggs is removed. That was the
problem that Chiron was experiencing. And then it has to be
packaged. It has to be tested to make sure that all of packages
have exactly the same amount of antigen in them. There are all
kinds of quality control steps that have to go on in there.
Everything has to work exactly right for that vaccine to be
available in September when we need it.
Mrs. Blackburn. Okay. Thank you very much.
Mr. Chairman, I yield back.
Mr. Whitfield. Thank you very much.
We will begin a second round. And I would recognize Mr.
Stupak for 8 to 10 minutes of questions.
Mr. Stupak. Thank you, Mr. Chairman.
And, Dr. Gerberding, in response to Mr. Burgess' questions,
you had indicated that the cost for the vaccine is--you gave
three different costs, 9.95, 13.25, and 24.50. Is that this
year's prices or last year's?
Ms. Gerberding. What I am quoting to you are catalog prices
for 2005 for three different manufacturers of vaccine. I would
be happy to provide you with the list of the catalog prices for
your record.
Mr. Stupak. Very good.
Mr. Stupak. Catalog price, is that the price the government
would pay for?
Ms. Gerberding. Generally we are able to negotiate a slight
discount off of those prices.
Mr. Stupak. If we want to put--and I think you used the
word overexpanding our pool of more and more people getting the
flu vaccine, and ideally we would like everybody to get it, I
thought you said. So, in a business model, wouldn't the more we
produce lower the cost per vaccine?
Ms. Gerberding. Ultimately that may be true. I think what
we are talking about is a market-driven process here. The more
people you vaccinate, obviously you can commoditize the vaccine
if you get up to a large enough population. If you were
thinking about the global community of people who need to be
vaccinated, we would be talking about large-scale and
potentially very cheap vaccine.
Mr. Stupak. How about just here in the United States?
Because I think earlier in your testimony you said we have
spent hundreds of millions to modernize a facility to develop a
new culture, to move from the egg to a cell culture. So that
would help drive down the cost of manufacturing; would it not?
Ms. Gerberding. That is an independent investment. We are
talking about apples and oranges here. One is the process, by
simply making more of what we already know how to make, and the
other is making something completely new. And the investments
we are making is a completely different manufacturing process
that would involve new factories and a new science and a new
regulatory approval process.
Mr. Stupak. Here is my problem. Those hundred millions came
from the U.S. taxpayer, right?
Ms. Gerberding. Correct.
Mr. Stupak. And if you look at the first chart you had up,
and the ones who get the immunizations first are the high-risk
group, people over 65.
Ms. Gerberding. Correct.
Mr. Stupak. And young babies probably under 2 years old,
right? And if you look at that, over 65, that means Medicare
pays, doesn't it?
Ms. Gerberding. That is correct.
Mr. Stupak. Under 2, most of that is Medicaid paid,
correct?
Ms. Gerberding. Not necessarily. It applies to all
children.
Mr. Stupak. Okay. Well, children are either covered--well,
private insurance, of course. But I think you would find most
of the children are probably covered who are getting these
shots through either CHIP program, Children's Health Initiative
Program, or through a Medicaid program. In my home State of
Michigan, that certainly is the case.
Ms. Gerberding. The children who do not have private
insurance are covered under something called the Vaccine For
Children Program. So it is a special program that applies to
all of the other childhood immunizations.
Mr. Stupak. So we have got another program then. Okay. The
point being, why can't then the government negotiate deeper
discounts then, if we are putting hundred of millions into the
manufacture to modernize the facilities, most of the costs or
the payments on these immunizations are coming through the
government on Medicaid, Medicare, CHIP or the children's
immunization program. I would think we could get bigger
discounts, because I am really bothered by the 17 percent
increase.
And just a thought there. If we--you also mentioned
something about 30 million in insurance. Is that 30 million set
aside to buy immunizations if we should run out in this
country? You mentioned 30 million in insurance. Do I understand
that right?
Ms. Gerberding. In this fiscal year we have $20 million
available to purchase bulk vaccine. And what that means is the
manufacturer at the end of the season can continue the
production, but not necessarily take that big vat of vaccine
and convert it into individual vials. So it is a very cheap
purchase because we buy it at an earlier production process.
Two things--well, three things could happen. One is we turn
out to need it, and we would need that late-season vaccine.
Maybe it is a bad season, maybe we've got a failure in somebody
else's manufacturing process and we need it. So they can go
ahead and complete the production and utilize it the way we
would the regular vaccine purchase.
The second thing is that we may not use it this year, but
by luck sometimes one of this year's strains is also the strain
in the next year's vaccine. So we are a step ahead of the
process; we have already purchased some vaccine for the
following year. And when it is in monovalent form like that, we
have got three different strains sitting in those formulations,
so there is a good chance that one or two of them will be able
to be used the following year.
The third thing could happen is that that wouldn't be the
case, and that would go to waste. But if we are wasting it, it
is a cheaper waste than buying the fully manufactured vaccine
and wasting that.
So it is a way for us to partition the risk to the
taxpayers, but the opportunity to develop a little more vaccine
at the end of the season if it turns out that we need it, and
in a year like this we would have liked to have had that.
Mr. Stupak. So in your strategies development and in your
policy development, do you have any monies then set aside in
case we do have a bad flu season; we use up everything we have,
and we have to get more into this country to help out that
high-risk population? Is there any backup plan?
Ms. Gerberding. We have, in addition to the $20 million I
mentioned for the monovalent, we have $20 million at least
proposed in the 2006 budget for vaccine purchase. It is not
specific to purchasing at any particular place or time, but we
will be negotiating contracts for that. We also purchased
through the Vaccines for Children Program that you mentioned
before a stockpile of influenza vaccine again so that if we end
up late in the season and we need that, the government has
purchased some to protect those children.
And, as Dr. Goodman has stated, we have a good chance of
getting an international manufacturer interested. And we are
not stopping there; we are obviously continuing to work with at
least two other ones to encourage them to get their licenses
and their applications.
Mr. Stupak. This $20 million for purchase and reserve that
you sort of are holding on, did you have this in reserve last
year, too? Did you have that amount of money, $20 million, in
reserve to purchase immunizations if you needed it last year?
Ms. Gerberding. We had a stockpile for the first time this
past year. So that was one step that had already been taken. We
also had a stockpile of drugs for the first time this past year
in part of our overall flu preparedness, not anticipating. And
then during the flu season, the additional doses were purchased
under the investigational new drug category, which is not the
optimal way to get vaccine, but if we don't have it any other
way, that is the resort we had to use.
Mr. Stupak. Well, when you purchased the IND, where was
that purchased from?
Ms. Gerberding. That was purchased from two companies, one,
the GSK purchase, and then I can't remember the--Berna Biotech.
Mr. Stupak. Berna Biotech, was that the Canadian company?
Ms. Gerberding. I think so.
Mr. Goodman. Swiss.
Ms. Gerberding. Right. Sorry. That is right, we didn't buy
the Canadian.
Mr. Stupak. So you have no objections to reimportation of
drugs then if it is necessary on this flu vaccine if we need
it.
Ms. Gerberding. This would not be considered reimportation.
This is purchasing vaccine from an international manufacturer
in a plant that we have certified as having good manufacturing
practices and a chain of custody of the product that would
assure our Americans that it arrived here safely.
Mr. Stupak. And we inspect drug manufacturers all over the
world, don't we, to make sure that they are safe and there is a
chain of custody, Correct?
Ms. Gerberding. If the drug is going to be sold in the
United States and licensed in the United States, I believe that
is----
Mr. Stupak. In fact, we get a lot of our drugs from India;
do we not, Dr. Goodman?
Mr. Goodman. Certainly it is an increasingly global market
with global manufacturing. One important difference here, of
course, is those, the GSK and the Berna Biotech that Dr.
Gerberding mentioned, were not U.S.-licensed vaccines. And so
they were purchased by the government basically for emergency
use, and they would have been used under the nonlicensed
category of investigational new drugs, so they would have
required informed consent by the recipients. So there is some
of the same issues, certainly, but these were not licensed
products.
Mr. Stupak. Sure. And my time is running short here. But we
have FDA inspectors all over the world inspecting plants all
over the world to make sure that they meet standards and
qualities, right?
Mr. Goodman. That is certainly increasingly the case.
Mr. Stupak. Sure. So the issue on reimportation is to make
sure we have people who can do the inspections and make sure
the chain of custody is intact, right?
Mr. Goodman. I think--I am not an expert in that field, I
am a biologics person. But certainly a critical requirement
would be to be sure the product is what you think it is, that
it was properly made, and that it has been in custody and
proper care. And that is a very resource-intensive----
Mr. Stupak. Let me ask you one more question. Mrs.
Blackburn brought up about the liability issue there and her
multistage strategy or whatever it was. In the vaccines that
are made for flu, does the Federal Government back up or
indemnify the manufacturer if there is a claim?
Mr. Gellin. There is an vaccine injury compensation program
that is defined by a vaccine that is given universally to
children. This year for the first year the influenza vaccine
was added to that list because of the recommendation for this
past year that all children 6 to 23 months of age receive it.
Mr. Stupak. So medical liability really shouldn't be an
issue in this, then, if it is being backed up or indemnified by
the Federal Government.
Mr. Gellin. Again, the flu vaccine is now included in the
program.
Mr. Stupak. So medical liability would not be an issue.
Mr. Gellin. Again, I am not an expert in that. There is
always the potential for people to go outside that program,
given the way it is designed, but it is there as really the
first stop.
Mr. Stupak. If we modernize the plants, we are the biggest
purchaser, we indemnify them for medical liability, I can't
figure out why we can't gain more entrance into the flu vaccine
area.
Mr. Whitfield. Thank you.
Just to follow up on Mr. Stupak for a minute, is the FDA
concerned that, in times of shortage, that State and local
agencies might look beyond the established U.S. manufacturers
to get a vaccine supply?
Mr. Goodman. Well, I think we recognize that with what
happened with flu last year, you know, if I were a Governor--I
was in a State not too long ago and worked with the State
health department as part of what I did. I can see that there
was really a desire to get vaccine quickly. I think what we are
concerned with is that any vaccine that is administered to the
American people meet the high standards they expect for safety
and efficacy. So if that were being done in a way that raised
concerns about that, we would be concerned.
Mr. Whitfield. But the policy right now is that, as I think
Dr. Gerberding explained, if you have to go out in these
emergency situations now, these plants are licensed, and you
have the custody issue; and, if not, then you have to have
informed consent. Is that correct, Dr. Gerberding? I mean,
under your insurance policy that you were discussing, you can
go out and buy additional vaccine and if there is a real need.
But you do that only under certain circumstances.
Ms. Gerberding. We are buying incompletely manufactured
vaccine as a backup.
Mr. Whitfield. Okay. At this time I would recognize our
doctor from Texas for 8 minutes of questions.
Mr. Burgess. Thank you, Mr. Chairman.
Well, let us continue on that line that Mr. Stupak just
brought up now on the vaccine injury compensation fund. Is that
only for children? If adults are immunized with the flu vaccine
and have an adverse reaction, are they also indemnified by the
vaccine fund?
Mr. Gellin. The program is designed around a vaccine, and
if a vaccine is recommended for all children or a group of
children, then anybody who receives that vaccine would be
covered by the program.
Mr. Burgess. Now, does that limitation of liability, would
that indemnify a company if they had thimerosal in their
vaccine?
Mr. Gellin. It is not an indemnification program; it is an
injury compensation program.
Mr. Burgess. Would that cover an injury that was purported
to be covered by thimerosal?
Mr. Gellin. There is a list of compensable reactions to
these vaccines, and that is not currently on the list of
adverse reactions to influenza vaccine.
Mr. Burgess. So if a family wished to bring a charge or a
case against a manufacturer for placing thimerosal in their
product, that would be outside the compensation range of the
injury fund, the vaccine compensation injury fund?
Mr. Gellin. I am sorry. I guess this gets beyond my
expertise and the nuance of the program. So I think we should
supply you with the details about that and about the program.
Mr. Whitfield. Did you want to respond to that, Dr.
Gerberding?
Ms. Gerberding. I think that anyone can bring a claim to
the injury compensation fund. Whether or not it would be
settled in favor of the claimant is something that would be
based on the merits of the claim. So that is the extent of my
knowledge of the program as well.
Mr. Burgess. Well, Mr. Stupak was making the point that
since there was complete release of liability, he didn't
understand why the manufacturers would not be in the game. But
it is my understanding that the additive in the flu vaccine, if
that is the target of the lawsuit, that that may be outside
what is covered by the vaccine injury compensation fund.
Ms. Gerberding. I think right now it is important to think
of risk in an even more comprehensive way. There is certainly
the risk to the individual who receives the vaccine, a risk
that the manufacturer experiences as the manufacturer of
vaccine that's caused the risk to an individual. But the risk
that is really in play this past year is the risk to the
manufacturer of not being able to produce vaccine and get it
licensed because the process and the methodology used is so
prone to problems. And we have seen this happen over and over
again.
You are starting with an egg, which is intrinsically not a
sterile product; you are growing something in it, and in the
end you have to end up with a vaccine that is free of any kind
of contamination. So just getting from the egg to the vaccine
is a very risky prospect from the standpoint of the people who
are manufacturing it. And I think that is one of the kinds of
risks that is very difficult to eliminate. You need an
insurance policy for that kind of risk to replace the profit
that was lost because your license was pulled due to a
manufacturing methodologic issue. And I am not aware that we
have that kind of insurance program for vaccine manufacturers.
Mr. Burgess. I am not either. We do it for farmers, I
think.
On the issue of the price increase, I guess what is being
referenced is a Wall Street Journal article from May 4, which
is today, and it talks about the 17 percent increase. The
actual dollar amount of that increase was $1.40 above 2004
prices and the first rise in 3 years, if I am reading this
article correctly. Any speculation on what amount of that price
increase is there because of liability concerns or other
manufacturing risk concerns?
Ms. Gerberding. I couldn't speculate about that. I think
that would have to be addressed to the manufacturer.
Mr. Burgess. Mr. Chairman, do we have any way of obtaining
that information?
Mr. Whitfield. We will submit that question for the record
and do some follow-up on it and see what we come up with.
Mr. Burgess. Well, the line of questioning previously
seemed to indicate an environment that was free of risk for the
manufacturer, a guaranteed purchase by the Federal Government,
and a guaranteed pool of purchasers. It looks to me to be a
field that is fraught with a great deal of more peril than was
previously outlined.
Mr. Stupak. Would the gentleman yield on that point?
Mr. Burgess. Well, I was going to say I will yield back my
time because I know the other side has some additional
questions. Thank you, Mr. Chairman.
Mr. Stupak. Would you yield on that point? It was Mrs.
Blackburn that brought up the liability issue with her
questions, multistrategy, as she called it. So I was trying to
probe the depth of it. And I knew that the Federal Government
does provide some funds there to patient protection. I am not
trying to get into a malpractice argument with you. That is for
another day.
Mr. Whitfield. But we will note the doctor's question, and
we will follow up on that and get that into the record.
Mr. Burgess. Well, it really wouldn't be a malpractice
question, it would be a products liability question, defective
product from the thimerosal standpoint.
Mr. Whitfield. Do you have any other questions?
Mr. Burgess. No, sir. I will yield back.
Mr. Whitfield. At this time I will recognize for 8 minutes
Ms. Schakowsky of Illinois.
Ms. Schakowsky. Thank you.
In 2004, knowing that a severe flu season without an
adequate supply of vaccine could result in a disaster,
especially among the elderly and the chronically ill and the
very young, Illinois Governor Rod Blagojevich began looking for
additional vaccine for Illinois. He asked a licensed regulated
wholesaler in Europe to see if they could find and secure
approved European flu vaccine on our behalf. After an intensive
search, the wholesaler found vaccine and began securing doses
to meet Illinois' request.
On October 25, Illinois officials sent a letter to the FDA
asking it to review and approve vaccine made by Aventis Pasteur
in France and GlaxoSmithKline in Germany. And 4 days later the
officials, Illinois officials, came and met in person with the
FDA to answer their questions. And that started a dialog
between Illinois experts and the FDA over the origin, custody,
storage of the vaccine, volumes of documentation. And while the
FDA didn't respond, Illinois, it gave the CDC approval to
import millions of doses from the very same German made
GlaxoSmithKline vaccine for use in the United States.
And then early December, after numerous exchanges between
Illinois experts and the FDA, Acting Commissioner Lester
Crawford stated in a press conference that Illinois had
answered their questions and provided all the information they
needed, and that the FDA would have a response very soon. As of
today, 5 months later, Illinois still has not received a
response from the FDA.
I would like an answer, Dr. Goodman. What went wrong, and
why can't Illinois, after its best effort in working with you,
come to an agreement on how to take care of its own
constituents, its own residents?
Mr. Goodman. Well, a couple of comments. I don't have all
the details on the correspondence between or communications
between the Office of Regulatory Affairs, the inspectorate
force, basically, who were working most intimately with
Illinois to document the nature of the vaccine. But what I can
tell you is we met very early on with the Illinois people. I
appreciate, and I told them at the time and so did others at
the FDA, the demands being made upon them and their desire to
get vaccine for their citizens. So we very much appreciate
that.
Ms. Schakowsky. That is all very nice.
Mr. Goodman. Well, we made the point very early on that
apparently the vaccine was extensively in distribution, was not
clearly--they were not clear about whose hands it had been in.
Some had been shipped to other countries. It was not in the
manufacturer's distribution. And we said to them that we would
work with them, but it was a very difficult task they would
have ahead of them to provide adequate documentation that the
vaccine was what it was, had been properly stored so that it
would be safe and effective. And another important point is
this is not U.S.-licensed vaccine, so that it would then have
to be used under IND.
My understanding is, to answer your question, that the
information--first of all, they told us we would provide that
information right away. It took quite some time to provide
information. The information was reviewed in the Office of
Regulatory Affairs. The message was given that there were
numerous gaps in the documentation.
Ms. Schakowsky. And why did Dr. Crawford state in a press
conference that Illinois had answered all their questions and
provided all the information that was needed?
Mr. Goodman. Well, again, my understanding from the Office
of Regulatory Affairs is that their last information given by
them to the representatives of the State--and I can't say
whether this was a letter or from whom or in what form--was
that the documentation provided had deficiencies; and that
given concerns about the safety of the vaccine, how it had been
handled, what it was, that additional information would be
needed. And I also understand that it was suggested and later
offered, I believe, through the Centers For Disease Control,
that vaccine that had been clearly under control, stored, and
in the manufacturer's control, which was why we worked on
getting that right away at the Secretary's request, would be
made available, in fact, to Illinois or others who wanted it
under the CDC's IND. So you had the opportunity for a well-
characterized, well-known vaccine that we knew to be safe,
where there had been extensive review of the manufacturing and
the pedigree of that vaccine. So I think we made a good-faith
effort together working with your folks.
I think there were deficiencies in the data. I think then,
when that was the case, we also made a good-faith effort to get
this other vaccine where there were not deficiencies in the
data and to make it potentially available. I would be happy to
talk more with you about it or----
Ms. Schakowsky. I think we need to talk more about it,
because I think there was a clear understanding in December
that Lester Crawford had clearly stated that we had--and
Illinois met all the requirements, and that still there was--
and that there would be an FDA response very soon, and that
none of that happened. So I hope that we can clarify that.
I had to step out for a little while, and I am just
wondering if you did finally answer the question that Mr.
Stupak had asked if we--and I am quoting now from the Wall
Street Journal: It also shows that the vaccine production
infrastructure remains nearly as fragile and outdated as it was
before last year's crisis.
Let me just say that, hearing Dr. Gerberding's numbers, it
sounds to me like even the middle case doesn't even begin to
meet what is--your statement of what is a public health need. I
understand demand and need are different, but what it also says
to me is that we need to promote getting the vaccine in a more
aggressive way to a large population that isn't even asking for
it. And, second, were they to ask for it, even under the very
best of scenarios, we cannot provide it. Now, so are we in as
good a shape, better shape, worse shape than we were last year?
Anybody?
Mr. Goodman. Well, I am happy to take the first crack at
that. I think we all recognize there is a clear problem with
the fragility of the flu vaccine manufacturing infrastructure.
I think there is some progress that has been made, but there is
still a problem. The progress that has been made is that, as
mentioned, GlaxoSmithKline, in part because of the work on the
IND, has stated that they are going to apply for U.S. Licensure
under the accelerated approval mechanism we provided. So they
expressed clear interest to enter the market for this year.
That is potentially more diversity. Another bit of progress is
the--while the jury is still out, the improvements that Chiron
has made in its manufacturing. Then I would go one step further
and say there are at least a couple of other manufacturers that
we have been working with who have indicated long-term interest
in the U.S. market.
But, yes, you are absolutely correct. Challenges remain
both in the underlying technology and in the market forces. And
it is almost a vicious circle, because if you can't provide a
stable vaccine supply, how can you continue to ramp up demand?
And if you don't continue to ramp up demand, how do you have a
stable supply? We are all living that, and we definitely
support things to occur on both ends, stabilizing the supply
and increasing uptake and demand.
It is helpful to realize that I think about 10 years ago
there were only about 20 million doses of flu vaccine
administered in the United States. So while it seems we have a
long way to go, and as a public health person I think we do and
we share that concern, there has been progress over a 10-year
period.
Mr. Whitfield. Ms. Schakowsky's time has expired. Do the
two of you want to respond to her last question, or do you
feel--okay.
One comment that I would just make on this Illinois
situation, and you can tell me if I am correct or incorrect,
but it was my understanding that the FDA, did they actually
receive appropriate drug master files on the vaccines from
Illinois?
Mr. Goodman. I would have to get back to you on the drug
master file. The drug master file would be what the
manufacturer possesses that says everything about the product.
I think--I would need to get back to you because there were at
least a couple different manufacturers involved. But the
manufacturers, to my knowledge, signaled a willingness to help
in this.
The issue that was definitely where there was a deficiency
was in the data that documented every--how that vaccine had
been handled after it left the manufacturer. And I think that
is where the Office of Regulatory Affairs had a safety concern.
Mr. Whitfield. Okay. Well, that concludes today's hearing.
I want to thank the witnesses for your patience. And we are
going to keep the record open for 30 days, and ask that any
questions for the record be submitted within 7 days to be
answered.
Obviously this is a particularly important subject, and
your testimony today, I think, provided enlightenment not only
for the committee members, but also for the general public. And
we do commend you for the work that you are doing and look
forward to working with you as we move forward to address this
important issue.
With that, the hearing is adjourned.
[Whereupon, at 5:12 p.m., the subcommittee was adjourned.]