[House Hearing, 108 Congress]
[From the U.S. Government Publishing Office]
THE NATION'S FLU SHOT SHORTAGE: WHERE ARE WE TODAY AND HOW PREPARED ARE
WE FOR TOMORROW?
=======================================================================
HEARING
before the
COMMITTEE ON
GOVERNMENT REFORM
HOUSE OF REPRESENTATIVES
ONE HUNDRED EIGHTH CONGRESS
SECOND SESSION
__________
NOVEMBER 17, 2004
__________
Serial No. 108-246
__________
Printed for the use of the Committee on Government Reform
Available via the World Wide Web: http://www.gpo.gov/congress/house
http://www.house.gov/reform
______
U.S. GOVERNMENT PRINTING OFFICE
97-448 PDF WASHINGTON : 2004
_____________________________________________________________________________
For Sale by the Superintendent of Documents, U.S. Government Printing Office
Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; (202) 512-1800
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COMMITTEE ON GOVERNMENT REFORM
TOM DAVIS, Virginia, Chairman
DAN BURTON, Indiana HENRY A. WAXMAN, California
CHRISTOPHER SHAYS, Connecticut TOM LANTOS, California
ILEANA ROS-LEHTINEN, Florida MAJOR R. OWENS, New York
JOHN M. McHUGH, New York EDOLPHUS TOWNS, New York
JOHN L. MICA, Florida PAUL E. KANJORSKI, Pennsylvania
MARK E. SOUDER, Indiana CAROLYN B. MALONEY, New York
STEVEN C. LaTOURETTE, Ohio ELIJAH E. CUMMINGS, Maryland
DOUG OSE, California DENNIS J. KUCINICH, Ohio
RON LEWIS, Kentucky DANNY K. DAVIS, Illinois
TODD RUSSELL PLATTS, Pennsylvania JOHN F. TIERNEY, Massachusetts
CHRIS CANNON, Utah WM. LACY CLAY, Missouri
ADAM H. PUTNAM, Florida DIANE E. WATSON, California
EDWARD L. SCHROCK, Virginia STEPHEN F. LYNCH, Massachusetts
JOHN J. DUNCAN, Jr., Tennessee CHRIS VAN HOLLEN, Maryland
NATHAN DEAL, Georgia LINDA T. SANCHEZ, California
CANDICE S. MILLER, Michigan C.A. ``DUTCH'' RUPPERSBERGER,
TIM MURPHY, Pennsylvania Maryland
MICHAEL R. TURNER, Ohio ELEANOR HOLMES NORTON, District of
JOHN R. CARTER, Texas Columbia
MARSHA BLACKBURN, Tennessee JIM COOPER, Tennessee
PATRICK J. TIBERI, Ohio BETTY McCOLLUM, Minnesota
KATHERINE HARRIS, Florida ------
MICHAEL C. BURGESS, Texas BERNARD SANDERS, Vermont
(Independent)
Melissa Wojciak, Staff Director
David Marin, Deputy Staff Director/Communications Director
Rob Borden, Parliamentarian
Teresa Austin, Chief Clerk
Phil Barnett, Minority Chief of Staff/Chief Counsel
C O N T E N T S
----------
Page
Hearing held on November 17, 2004................................ 1
Statement of:
Gerberding, Dr. Julie L., Director, Centers for Disease
Control and Prevention; Dr. Anthony S. Fauci, Director,
National Institute of Allergy and Infectious Diseases; and
Dr. Lester M. Crawford, Acting Commissioner, Food and Drug
Administration............................................. 137
Pien, Howard, president, chief executive officer, and
chairman of the board, Chiron Corp.; Kathleen Coelingh,
senior director, regulatory and scientific affairs,
MedImmune, Inc.; Dr. Robert Stroube, Virginia State health
commissioner, Association of State and Territorial Health
Officials; and Dr. Jerome Klein, professor of pediatrics,
Boston University School of Medicine....................... 245
Letters, statements, etc., submitted for the record by:
Burgess, Hon. Michael C., a Representative in Congress from
the State of Texas, prepared statement of.................. 404
Coelingh, Kathleen, senior director, regulatory and
scientific affairs, MedImmune, Inc., prepared statement of. 266
Crawford, Dr. Lester M., Acting Commissioner, Food and Drug
Administration, prepared statement of...................... 192
Cummings, Hon. Elijah E., a Representative in Congress from
the State of Maryland, prepared statement of............... 392
Davis, Chairman Tom, a Representative in Congress from the
State of Virginia, prepared statement of................... 5
Fauci, Dr. Anthony S., Director, National Institute of
Allergy and Infectious Diseases, prepared statement of..... 170
Gerberding, Dr. Julie L., Director, Centers for Disease
Control and Prevention, prepared statement of.............. 140
Klein, Dr. Jerome, professor of pediatrics, Boston University
School of Medicine, prepared statement of.................. 287
Kucinich, Hon. Dennis J., a Representative in Congress from
the State of Ohio, prepared statement of................... 396
Lantos, Hon. Tom, a Representative in Congress from the State
of California, prepared statement of....................... 308
Maloney, Hon. Carolyn, a Representative in Congress from the
State of New York, prepared statement of................... 390
Mica, Hon. John L., a Representative in Congress from the
State of Florida, article dated October 23-24, 2004........ 221
Owens, Hon. Major R., a Representative in Congress from the
State of New York, prepared statement of................... 309
Pien, Howard, president, chief executive officer, and
chairman of the board, Chiron Corp., prepared statement of. 248
Shays, Hon. Christopher, a Representative in Congress from
the State of Connecticut, prepared statement of............ 306
Stroube, Dr. Robert, Virginia State health commissioner,
Association of State and Territorial Health Officials,
prepared statement of...................................... 278
Towns, Hon. Edolphus, a Representative in Congress from the
State of New York, prepared statement of................... 387
Watson, Hon. Diane E., a Representative in Congress from the
State of California, prepared statement of................. 398
Waxman, Hon. Henry A., a Representative in Congress from the
State of California:
Memo dated November 17, 2004............................. 10
Prepared statement of.................................... 130
THE NATION'S FLU SHOT SHORTAGE: WHERE ARE WE TODAY AND HOW PREPARED ARE
WE FOR TOMORROW?
----------
WEDNESDAY, NOVEMBER 17, 2004
House of Representatives,
Committee on Government Reform,
Washington, DC.
The committee met, pursuant to notice, at 1:05 p.m., in
room 2154, Rayburn House Office Building, Hon. Tom Davis
(chairman of the committee) presiding.
Present: Representatives Davis, Shays, Mica, Duncan, Deal,
Murphy, Waxman, Lantos, Owens, Towns, Sanders, Maloney,
Cummings, Kucinich, Tierney, Clay, Watson, Van Hollen,
Ruppersberger, Norton, Cooper, and McCollum.
Staff present: Melissa Wojciak, staff director, David
Marin, deputy staff director/communications director; Keith
Ausbrook, chief counsel; Ellen Brown, legislative director and
senior policy counsel; Jennifer Safavian, chief counsel for
oversight and investigations; Anne Marie Turner, counsel;
Robert Borden, counsel/parliamentarian; Robert White, press
secretary; Drew Crockett, deputy director of communications;
Susie Schulte, professional staff member; Teresa Austin, chief
clerk; Sarah Dorsie, deputy clerk; Allyson Blandford, office
manager; Corinne Zaccagnini, chief information officer; Phil
Barnett, minority staff director; Kristin Amerling, minority
deputy chief counsel; Karen Lightfoot, minority communications
director/senior policy advisor; Anna Laitin, minority
communications and policy assistant; Sarah Despres and Naomi
Seller, minority counsels; Richard Butcher and Josh Sharfstein,
minority professional staff members; Earley Green, minority
chief clerk; and Jean Gosa, minority assistant clerk.
Chairman Tom Davis. Good morning. A quorum being present,
the Committee on Government Reform will come to order. I want
to welcome everybody to today's oversight hearing regarding
this year's U.S. influenza vaccine supply.
As most are now aware, on October 5, 2004, the Medicines
and Healthcare Products Regulatory Agency, United Kingdom's
version of the U.S. Food and Drug Administration, suspended
Chiron Corp.'s manufacturer's license for a period of 3 months.
Chiron planned on delivering 46 to 48 million doses of flu
vaccine, almost half of the U.S. supply.
This committee's investigation into the issues surrounding
the flu vaccine shortage began at a flu pandemic hearing in
February of this year. The committee informed U.S. health
officials of its concern that Chiron did not have a
manufacturing plant located within the United States. So should
a flu pandemic occur, it was theorized that the U.K. could
nationalize Chiron's vaccine supply, resulting in the loss of
half of our national supply.
At an emergency hearing on October 8, 2004, the committee
discussed contributing factors to the flu vaccine shortage, how
the government and vaccine manufacturers were responding to and
managing the crisis, and what steps would be taken to prepare
for next year's flu season.
As a result of testimony at these two hearings, Ranking
Member Henry Waxman and I sent a letter to the FDA requesting
documents that would indicate whether FDA knew about the
problems at the Chiron facility and whether FDA responded
adequately.
As part of this committee's investigation, I led a
congressional delegation to London last week to meet with top-
ranking officials from the MHRA and Chiron. The committee also
conducted an extensive meeting with FDA officials in Washington
to discuss FDA documents and the committee's findings from
meetings held in London. These meetings were extremely
productive, provided the committee with a timeline of events
leading up to October 5, 2004 the standard protocols used by
MHRA and FDA, and the steps all parties involved are taking to
prevent future vaccine shortages.
The FDA documents and investigative meetings held by the
committee confirmed several key facts. First and foremost, FDA
was unaware prior to October 5, 2004 that MHRA would suspend
Chiron's manufacturing license.
On October 25, 2004, Chiron contacted the FDA to alert the
agency there may be a delay in its vaccine shipment, as
contamination was located in some lots of Chiron's flu vaccine.
All documents and meetings confirm that FDA followed routine
protocol in responding to Chiron's initial contact with FDA and
continued to follow protocol with each step the agency took
after October 25th.
Chiron also notified FDA that it had conducted an internal
failure investigation to discover how the contamination
occurred. It is standard protocol for FDA to have a
manufacturer's failure investigative report in hand when
conducting an inspection. The FDA uses that report in
determining cause and the report serves as a roadmap for the
inspection. Chiron informed FDA that it would receive the
internal report the week of October 4, 2004. FDA has informed
the committee that it believed this was a reasonable timeframe.
During this time, FDA was in constant communication with
officials from Chiron and immediately alerted the Centers for
Disease Control and Prevention about the delay in Chiron's
shipment.
Unfortunately, the internal report was not provided to FDA
until after Chiron's license suspension. The MHRA, however, was
provided with Chiron's findings on September 24, 2004. As a
result, MHRA concluded its final investigative visit to Chiron
on September 30, 2004. The FDA has since reviewed the report
and instructed committee staff that had the agency received the
draft report sooner, the Chiron facility would have been
reinspected, whether or not MHRA suspended Chiron's
manufacturing license.
FDA, MHRA, and Chiron all agree that Chiron's license
suspension resulted from systematic problems within Chiron's
Liverpool facility, based on a lack of manufacturing oversight
and execution. In addition, all parties agree that prior
inspections conducted by both FDA and MHRA at the Chiron
facility did not foreshadow the license suspension. While some
issues at the facility continued from 2003 until September
2004, Chiron's license suspension wasn't based on contamination
in flu vaccine lots or other issues that were addressed in
previous inspections. It would be inappropriate to imply that
problems at the Chiron facility in 2003 recurred in 2004 and
contributed to the closure of the facility.
Questions have been asked as to why FDA was kept in the
dark regarding Chiron's license suspension until October 5th.
Pursuant to the U.K.'s Medicines Act, MHRA is prohibited from
sharing commercial information without the consent of the
manufacturer involved. FDA, MHRA, and Chiron all informed
committee staff that it is widely accepted and understood that
the two agencies do not discuss their own actions with regard
to companies over which they each have jurisdiction. In
addition, it would be standard procedure for Chiron not to
discuss this interaction with FDA or MHRA with the other
agency. Since October 5th, Chiron has permitted FDA and MHRA to
communicate on all issues.
This investigation has been conducted in a bipartisan
manner. Politics has no place in the public health arena. I
hope that this spirit of cooperation isn't threatened today by
those who choose to ignore standard FDA protocol, accepted by
vaccine manufacturers worldwide, and place the sole blame for
the flu vaccine shortage on a single agency, rather than taking
an objective look at all of the facts presented during the
committee's investigation. If protocols need to be tweaked,
however, then let us talk about tweaking them.
After all, should FDA be held accountable for decisions
made by Chiron without its knowledge or for actions taken by
MHRA that were legally protected by the law of the U.K.? If the
committee spends too much time placing blame and pointing
fingers, we will be unable to look to the future to ensure that
the United States has an adequate flu vaccine supply. Let's let
experience be our teacher.
My main goals in this investigation are to understand the
lessons learned from the events leading up to and occurring
since October 5, 2004, and, most importantly, to work
vigilantly with U.S. health officials and private industry to
ensure that a similar situation does not occur in the future.
Based on my findings with the FDA, MHRA, and Chiron, I am
optimistic that Chiron will be able to produce vaccine for next
year's flu season. The license suspension didn't prohibit
Chiron from procuring its startup materials for next year. As
of today, Chiron has contracted and paid for its egg supply for
the 2005-2006 flu season. MHRA is extremely pleased with the
remediation plan that Chiron has submitted, and a followup
inspection will be conducted in late December to evaluate
Chiron's progress.
It is important to recognize there is a need to expand the
current number of FDA approved flu vaccine manufacturers and to
bring those manufacturers into the U.S. markets. We are going
to work on legislation designed to provide incentives to flu
vaccine manufacturers in hopes that we can stimulate the
vaccine market domestically.
Since our October 8, 2004 hearing, both Aventis Pasteur and
MedImmune have been able to produce additional doses of flu
vaccine. FDA has also identified and negotiated for
approximately 5 million doses of flu vaccine from foreign
manufacturers. Additionally, the Nation has a supply of enough
antiviral medicines to treat about 40 million people. These
antiviral drugs can be used to prevent or treat the flu if
symptoms are identified early.
Our witnesses today will discuss how U.S. health officials
are procuring and adequately distributing the flu vaccine to
the high-risk population and preparing for next year's flu
season, and what incentives can be provided to manufacturers to
ensure a stable annual flu vaccine supply.
In addition, I am pleased that Howard Pien, the president
of Chiron Corp., is present to speak publicly for the first
time since October 5, 2004. I know we are anxious to hear his
testimony as to Chiron's remediation plan and how Chiron is
moving forward in preparation for next year's flu season.
We have an excellent roster of witnesses, and I would like
to thank all of them for appearing before the committee, and
look forward to their testimony.
[The prepared statement of Chairman Tom Davis follows:]
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Chairman Tom Davis. I would now like to yield to Mr. Waxman
for an opening statement.
Mr. Waxman. Thank you, Chairman Davis, for holding this
hearing on the flu vaccine shortage. You and I share the goal
of establishing a healthy vaccine supply in the United States,
and effective government oversight is an important part of this
process.
This year's flu vaccine crisis raises three important
oversight questions.
The first question is how the United States came to depend
on just two companies for the flu vaccine. The Institute of
Medicine, the Government Accountability Office, the National
Vaccine Advisory Committee have all issued reports exposing the
weakness of our national vaccine infrastructure, and we can't
afford to ignore their recommendations any longer. And they
have been making recommendations since the year 2001.
The second question is why the vaccine shortage led to such
confusion and chaos. In a series of reports over the last 4
years, GAO repeatedly warned that the United States does not
have a plan to ensure that the highest risk people are
immunized in the event of a shortage. The seniors who have been
standing in lines for hours trying to get a flu vaccine know
that GAO was right.
And the third question is the primary subject of today's
hearing: Did FDA do its job to protect the U.S. vaccine supply?
Since the vaccine shortage began, senior administration
officials, including Acting FDA Commissioner Lester Crawford,
have been reassuring the public that the FDA made no mistakes
and did everything possible to protect the vaccine supply.
Today we will evaluate those claims.
On October 13th, Chairman Davis and I asked FDA to provide
copies of documents relating to its oversight of the Chiron
vaccine plant in Liverpool, England. This is the plant that
British regulators shut down on October 5, causing the United
States to lose approximately half of its supply of the flu
vaccine.
We have now received and reviewed over 1,000 pages of
documents. We have also met with FDA officials, and the
chairman traveled to England with majority and minority staff
to interview British and Chiron officials.
The documents show that FDA failed to provide effective
oversight. Expert scientists at FDA knew about serious problems
at the Liverpool facility in June 2003, but there was not
sufficient leadership at the agency to ensure that they were
fixed.
My staff prepared a background memorandum for this hearing
that describes the documents and their significance in detail,
and I ask that this memorandum and the redacted versions of
documents cited in the memorandum be made part of the hearing
record.
Chairman Davis. No objection. Let me just add that I think
that all records in the binders before the Members, majority
and minority, ought to be made part of the record, and if there
is no objection, so ordered.
[The information referred to follows:]
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Mr. Waxman. The Chiron plant in Liverpool was not an
ordinary FDA-regulated facility. It is a facility with a
history of contamination problems that makes half the supply of
the U.S. flu vaccine. The plant should have received the
highest priority from the Food and Drug Administration.
Yet the agency ignored glaring problems at the facility and
missed repeated opportunities to correct them.
Mr. Chairman, you said you don't want us to point fingers
and look at the past, let us look at the future. You even, I
thought, said you don't want partisanship invoked in our
hearings. I don't know what is partisan about criticizing what
has led to, in my view, the situation we are facing today. If
you don't learn from the past, you are not going to correct
these problems for the future.
I have been in Congress for 30 years. Throughout this
period, oversight of FDA has been one of my highest priorities.
I drafted many of the major laws that the agency implements,
including the Orphan Drug Act, the Hatch-Waxman Act, the
Nutrition Labeling and Education Act, the Safe Medical Devices
Act, the user-fee law that accelerated drug approvals, and the
Food Quality Protection Act. That is why I have become so
concerned about how the agency has performed in recent years.
What we are witnessing is the dismantling of FDA's
enforcement and oversight capabilities. In area after area, the
agency is failing to enforce the public health laws that
Congress enacted. Enforcement actions for misleading drug
advertisements have dropped 70 percent since 2001. Enforcement
actions at vaccine plants and other manufacturers of biologic
drugs have dropped over 80 percent. Key food labeling laws are
being ignored.
And there is no better example of what is wrong at the FDA
than its failures at the Chiron vaccine facility.
The story told in the FDA documents begin in June 2003,
when a team of FDA inspectors visited the Liverpool facility
and found 20 serious problems at the plant, including bacterial
contamination and poor sanitary practices. The FDA experts who
conducted the inspection recommended the agency take official
enforcement action against the company. Yet this recommendation
was rejected. FDA downgraded its response and asked the company
to make only voluntary reforms.
FDA's justification for failing to cite the facility is
that the agency thought conditions were improving. But
conditions weren't improving, they were deteriorating. Over the
next 16 months, as production at the facility increased, the
problems found in June 2003 mushroomed. Yet during this entire
period, the FDA never once revisited the plant to see if Chiron
was correcting its problems and making safe vaccines.
Incredibly, FDA remained passive even after October 25, 2004,
when Chiron disclosed that millions of doses of vaccine were
contaminated by a potentially lethal form of bacteria.
A responsible regulator would have inspected the plant,
demanded to review its production records, and convened high-
level meetings of the agency's top experts. That is exactly
what the British regulators did. A senior British health
official summed up their philosophy as ``seeing is believing.''
By contrast, FDA conducted oversight by conference call,
trusting a stream of false assurances by Chiron that the plant
had no serious problems. FDA conducted no inspection; it
reviewed no plant records; and it was caught completely by
surprise when British regulators shut down the plant on October
5.
FDA's laxity has had a heavy cost. If FDA had ensured that
the problems identified in June 2003 were fixed, this year's
flu crisis might never have happened. And if FDA had responded
aggressively to the contamination problems in August, our
public health system would have had critical extra weeks to
prepare for the shortage and to avoid the chaos that ensued in
October.
It is essential for FDA to learn from its mistakes. But, so
far, the administration has been unwilling even to admit them.
In recent weeks, the President, the HHS Secretary, the Acting
FDA Commissioner have all reassured the public that FDA did
everything right. The Acting Commissioner has even indicated he
would do it all over again, the same way.
And I might point out that all those assurances, given all
before the election, might be viewed as partisan, because there
at least we were facing election. We don't have an election
now; the election is over. So if we are critical of something
that is going on through oversight, that shouldn't be attacked
as partisan.
After the flu crisis broke, Dr. Crawford told the public
that the June 2003 inspection had ``no relevancy'' to the
problems found in 2004. He said that FDA monitored the actions
of Chiron and assured that the violations found in 2003 were
corrected. And he said that the United States and British
regulators had acted ``in synchrony.''
Well, none of these statements are true. In this
administration, inconvenient facts are simply ignored. This is
a dangerous way to govern and is particularly hazardous for the
public health.
I expect the chairman may disagree with me today about the
interpretation of some of the FDA documents. That is his right.
But even as we disagree over specifics, I want to commend the
chairman for his approach to this hearing. He has asked for the
right documents, he has worked with us to ensure that we can
release redacted copies so that Members and the public can
judge their significance for themselves. That is exactly the
right way to approach this important hearing. And I hope, after
we have had a chance to hear the testimony and ask the tough
questions, that we will feel better informed about what
happened to make sure that it doesn't happen again.
Thank you, Mr. Chairman.
[The prepared statement of Hon. Henry A. Waxman follows:]
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Chairman Tom Davis. Thank you.
I know a lot of Members would like to make opening
statements, but if we go through this, we will never get to our
panel; and our conference is still going on. So what I would
ask is we will give Members a week to submit written statements
for the record and, of course, on the questions they can make
statements and use their time to do that.
We are going to move to our first panel of witnesses. Dr.
Julie Gerberding, the Director of the CDC; Dr. Anthony Fauci,
the Director of the National Institute of Allergy and
Infectious Diseases; and Dr. Lester Crawford, the Acting
Commissioner of the Food and Drug Administration. They are
going to discuss efforts being taken at the Federal level to
manage the flu vaccine crisis. They will also describe their
efforts to coordinate distribution with State and local
authorities, and what steps are being taken in preparation for
next year's flu season.
It is our policy to swear all witnesses in. You have all
been here before, so if you would please rise and raise your
right hands.
[Witnesses sworn.]
Chairman Tom Davis. Thank you very much.
Dr. Gerberding, we will start with you. As you know, we
have a light here. Your entire statement is in the record, and
I can tell you that our staff and Mr. Waxman's staff have been
through the written testimony. We would like you, if you could,
to try to limit your testimony to 5 minutes. You have a light
in front of you. When the light turns orange, 4 minutes are up;
when it is red, 5 minutes are up. And when it is red, if you
could move to completion as quickly as possible. I don't want
to cut you off if you think there is something you need to say,
because this is televised and people are watching, but we are
conscious that we have a lot of questions and giving ample time
to amplify at that point.
Dr. Gerberding, thank you for being with us. Please go
ahead.
STATEMENTS OF DR. JULIE L. GERBERDING, DIRECTOR, CENTERS FOR
DISEASE CONTROL AND PREVENTION; DR. ANTHONY S. FAUCI, DIRECTOR,
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; AND DR.
LESTER M. CRAWFORD, ACTING COMMISSIONER, FOOD AND DRUG
ADMINISTRATION
Dr. Gerberding. Thank you. And I thank you and the staff of
the committee for their incredible interaction and
professionalism in helping us prepare and be responsive to this
hearing.
CDC is in a situation where we are faced with two big
goals. One is to do our part to ensure that we do have a modern
vaccine available to everyone who needs it that is safe,
effective, affordable, and accessible, and is produced in a
domestic manufacturing process that is reliable and robust. We
have a second urgent goal, and that is to assure that the
vaccine we do have this year gets to the people who need it the
most as quickly as possible.
And I would just like to start by thanking some very
important health protection heroes who have been doing their
part. First and foremost, I thank the people who have been
patiently waiting in lines and persistently trying to find
vaccine. I am sorry that they are in this situation. We are
doing everything we can to distribute the available vaccine
that is out.
I also thank the people who have stepped aside to let those
who need the vaccine get it. I am incredibly appreciative of
Aventis, who has collaborated with CDC's allocation plan.
Aventis, Chiron and the distributors who have made proprietary
information available to health officials so that we can do a
good job of targeting the vaccine.
Most importantly, I thank the true heroes of this whole
process, which are the State and local health officials who
have been working around the clock to assess the needs, assess
the flu situation in their jurisdictions, and make hard
decisions about where to allocate vaccine at the local level.
On the next graphic I have a picture of the current flu
situation as of the end of a week ago. The current situation is
good news: the season is not off to a fast start. We have local
flu activity or sporadic flu activity in many States; we still
have some States with no flu activity.
But as we pointed out in the next graphic, flu is very
unpredictable. The peak months of flu activity is very
unpredictable. February is the most common peak, but it can be
earlier or later than that. We also know that demand for flu
vaccine is unpredictable. We have seen, this year, a great
increase in demand. Certainly we have learned that the supply
is unpredictable. The current influenza activity suggests that
situation is getting us where we have a little more time to get
vaccine out, but we are not resting until we have every dose
allocated.
On the next graphic I have just put an organizational chart
of the CDC operation. We have activated our Emergency Operation
Center to handle the logistics of the flu season this year. It
involves several hundred people across CDC and public health
agencies who are working on various tasks. First and foremost
among them is allocating vaccine. CDC is using about 20 times
more dollars for flu this year than we did in 2002, so we are
doing everything we can to utilize those dollars and achieve
the best possible flu preparedness that we can.
In August, when we learned of the shortage, we purchased
vaccine for the stockpile in addition to those doses that we
had purchased earlier in the year. We also increased our supply
of antiviral medication for the stockpile. And more recently,
after the loss of the vaccine was noted in October, we have
increased by 5 million treatment courses antivirals for the
stockpile. We have also, in August, initiated a survey to
assess States' preparedness and contingency planning for
reprioritization and reallocation of vaccine, and took a number
of steps within the agency to have some contingency for worst-
case scenario. However we were operating on the premise that
the most likely scenario is that ultimately we would end up
with an unprecedented supply of vaccine.
On the next graphic I just have given a very few snapshots
of the kind of traditional flu tracking we do at CDC. This
involves people across our health agencies. We do laboratory
typing, State-based typing, mortality tracing of both adults
and pediatric populations.
But on the next graphic I have demonstrated some of the new
innovations that we are utilizing this year that never have
been used before to track flu. Chief among them is an ongoing
household survey where we can assess people's vaccine status on
an ongoing basis. In the first week of November, through the
household survey, we were able to determine that our targeting
efforts are working. Only 4 percent of low-priority patients
have been vaccinated this year, and for those that need it
most, including the seniors over age 65, we have more than 26
percent vaccine coverage, which is about where we would be at
the midpoint of the flu season.
The last graphic really illustrates the most important
component of all, and that is that flu is a preventable
illness. Vaccine is the most important component of prevention,
but there are other steps that we have to focus on this year as
well, including prevention of person-to-person transmission,
respiratory hygiene, hand hygiene, and, of course, antivirals.
For people who cannot get the flu vaccine but need it, it is
very important that they seek medical attention at the earliest
onset of flu, because antiviral drugs can treat flu and prevent
serious complications. We want to make sure that word gets out
widely. And, of course, we are also preparing for a worse flu
season than usual through other interventions at the community
and institutional level if we need them as we go down the road.
There are a number of things ongoing across the agency, and
we really appreciate the support of Congress in helping us get
there. We know we need to do more. We know that we have
requested $100 million in the 2005 budget to modernize our
vaccine strategy, and we look forward to working with you in
the committee and others on how we can do this expeditiously
and successfully. Thank you.
[The prepared statement of Dr. Gerberding follows:]
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Chairman Tom Davis. Thank you.
Before we get to Dr. Fauci, Mr. Waxman.
Mr. Waxman. Dr. Fauci, before we hear from you, I want to
express my feelings, and I think the feelings of the members of
this committee, about the loss, and sudden loss, of a leader in
infectious diseases, your Deputy, Dr. John La Montagne.
Members may not have known him personally, but he was a
person from whom we all benefited. He worked on issues such as
flu vaccination, biodefense research, malaria, and
tuberculosis. He was held in the highest esteem by all of his
colleagues. He had an exemplary public service record. I know
it is a loss to you, and I think to the country, that he has
suddenly passed away, and I wanted to extend my condolences.
Chairman Tom Davis. And I concur with that.
Dr. Fauci. Thank you very much, Mr. Waxman, Mr. Chairman,
and members of the committee. We really appreciate the
recognition that you have given to John La Montagne. It is a
fact that John was one of the leaders in influenza vaccine
research and, in fact, when he first came to the National
Institutes of Health almost 30 years ago, he was the first
influenza program officer in our research enterprise. So I
think he would be particularly interested in this hearing were
he here today, and thank you for your recognition.
Thank you, Mr. Chairman. I would like to take my time
allotted to me now to talk to you a bit about the research
approach toward tackling and meeting the challenge of
influenza, both the immediate challenge and the long-range
challenge, including that of pandemic flu.
As shown on this first poster, the NIH influenza research
is one of the components of the Department of Health and Human
Services' comprehensive program involving surveillance,
regulation, and research to not only understand the influenza
virus and the disease's cause, but also to help us partner
better with industry in order to overcome some of the
challenges that we have been meeting over these past several
months.
The research endeavor is comprised of both basic research;
research capacity; a bit of surveillance, which, as you know,
is fundamentally what the CDC does; but the end point is to
develop vaccines, therapeutics, and diagnostics.
This particular slide showing the influenza funding I think
is very telling, because it shows the effort that has been put
in under the leadership of Secretary Thompson at the Department
in expanding our capabilities. As you can see, in 2001 our
research endeavor was about $20 million, and the President's
budget for 2005 is approximately $66 million, a clear, rather
impressive increase in resources.
Some of the scientific issues that were tackled are of
importance to the discussions that are taking place here today.
Many of you have heard of the terminology ``reverse genetics.''
I will try to simplify that for you.
This was a technique that was developed by NIH grantees,
and what this technique does, it takes some of the uncertainty
out of finding and isolating the seed virus to grow for a
vaccine. And when you get a virus like isolated this year, the
H5N1 from Asia, and you want to grow that to develop a pilot
lot, you generally put a vaccine that is well adapted to
growing in eggs, which is the main medium of growing, together
with the vaccine in question, hoping that they will naturally
reshuffle their genes so that you have the component of the
virus in question within the framework of a virus that you know
from year after year grows well.
Reverse genetics circumvents that; it allows you to
actually pick out the genes and deliberately put them together
to form a hybrid type of a virus that we call a reassortment, a
molecular version of the reassortment, where you deliberately
do it yourself. That is how we isolated and got the H5N1 that
we are now preparing for a vaccine in the event of a pandemic
flu.
The next slide shows the two major research endeavors that
are ongoing now to tackle the question of how we can have
alternatives to egg-based vaccine, and that is the development
of cell culture vaccine production and recombinant DNA
technology. Hopefully we will get a chance to discuss this
during the question period.
Another important component of tackling influenza is what
we do with therapies, therapies that are for the actual
treatment of influenza as well as those that can be used for
prophylaxis or prevention. There are four drugs that are
available today against different targets. Three of them are
used for prevention and all of them can be used for treatment.
We need a more robust pipeline to be able to have in our
armamentarium other drugs in the event of the development of
resistance to these drugs by the influenza virus. And we know
from experience that whenever you treat a microbe over a period
of time, sooner or later there will be resistance. But we do
have drugs, as was mentioned by Dr. Gerberding, such as Tamiflu
and Rimantadine in our strategic national stockpile, with in
fact many more doses now being prepared for that stockpile.
And finally let me just mention a word of how we use the
research enterprise to approach the pandemic flu threat that is
an ever-looming threat. We know that this is occurring in Asia
right now. H5N1 is a virus that has already infected 44 people
and killed 32. The good news is that it has not yet learned to
effectively transmit from person to person; there is only one
documented case.
But if we use history to tell us what microbes can do,
sooner or later either this virus or a related virus might
learn that. So there are some research issues that need to be
addressed that will help us to be able to meet that challenge.
They are listed here. One is to isolate that virus, which
we, in collaboration with the CDC and the WHO, last year did,
and we did it by the reverse genetics technique that I
introduced you to just a moment or two ago. We are developing
pilot lots of the H5N1 and other bird flus. By pilot lots we
mean small amounts, 8,000 to 10,000, that can be used in
clinical trials, as shown on the third bullet.
Those clinical trials will begin anywhere from January up
to and including March or April; and this has been in
association with the purchase by the Department of 2 million
doses of H5N1 from Aventis-Pasteur to be able to have in our
stockpile, should we need it. And, finally, the continual
screening and development of new therapeutics.
So, in summary, as part of the broad comprehensive approach
of the Department, the NIH research endeavor will hopefully
continue to contribute productively to the challenge that we
will inevitably meet. Thank you, Mr. Chairman.
[The prepared statement of Dr. Fauci follows:]
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Chairman Tom Davis. Thank you very much.
Dr. Crawford, thank you for being with us.
Mr. Crawford. On August 25, 2004, Chiron informed FDA that
the company had discovered bacterial contamination in eight
lots of final vaccine product for this year's flu supply, and
advised that they were already investigating the problem to
determine the root cause of the contamination. At the same
time, they proceeded to quarantine all of the vaccine lots
while they retested the product.
In September 2004, FDA, CDC, and Chiron scheduled weekly
conference calls to discuss the status of the firm's
investigation. During these calls, they advised FDA that they
had identified the cause of the contamination, that it was
confined to specific vaccine lots. During their investigation,
Chiron informed FDA that the results of the retesting were
negative. They planned to submit a final investigative report
to FDA during the week of October 4th.
It is important to recall that on September 28th Chiron's
chief executive officer advised the Senate Special Committee on
Aging, ``As of September 27th, it remains Chiron's expectation
that between 46 million and 48 million Fluvirin doses will be
delivered to the U.S. market beginning in early October.''
On the morning of October 5, 2004, the British regulatory
organization, MHRA, announced a 3-month suspension of Chiron's
license to manufacturer influenza vaccine. FDA had no prior
knowledge of that intention, to suspend the firm's license. The
chief executive of MHRA indicated that they did not have the
legal authority to notify FDA before the October 5th
suspension.
Upon learning of the suspension, FDA contacted both Chiron
and the MHRA. Chiron indicated to FDA that it believed it had
satisfactorily addressed MHRA's inspectional findings. However,
the British expressed serious concerns about Chiron's vaccine
stocks and the company's ability to assure the safety of the
vaccine. FDA immediately dispatched a senior team of scientists
to the U.K. to meet with company officials and MHRA, and to
inspect Chiron's Liverpool manufacturing facility.
On October 15, 2004, after completing its inspection, FDA
determined that it could not adequately assure that Chiron's
vaccine met our safety standards. As a result, Chiron will not
supply any influenza vaccine to the U.S. market for the 2004-
2005 flu season.
In coordination with others at the Department of Health and
Human Services, we have been actively exploring all viable
options to secure additional dosage of flu vaccine to provide
more Americans protection against the flu. Through these
efforts, we have been able to increase the available supply of
licensed flu vaccines for the U.S. population to 61 million
doses for this flu season. We have also been contacting
manufacturers worldwide in an effort to identify increased
supplies of antiviral medications that will provide further
protection and treatment for Americans during this flu season.
Next year, Aventis-Pasteur believes they have the
capability of producing the same or more doses of the influenza
vaccine. In addition, MedImmune has indicated that it has the
capability to produce 10 million doses of FluMist for the 2005-
2006 season and as much as 40 million doses by 2007.
In partnership with the MHRA, we will continue to work with
Chiron in an effort to bring them back online for next year's
flu vaccine production. We are also encouraging foreign
licensed manufacturers to apply for U.S. licensure, and we will
work to help them achieve this goal.
Looking further ahead, we must develop more efficient ways
to produce flu vaccine so that we have the flexibility to deal
with shortages or unexpected problems. The Department has
requested $100 million for fiscal year 2005 to shift vaccine
development to new cell culture technologies, as well as to
provide for year-round availability of eggs for egg-based
vaccine. We urge Congress to fully fund the $100 million
requested, and we are encouraged by the positive response from
Congress on this important request.
To help manufacturers overcome challenges such as the
vaccine development problems that Chiron is experiencing, FDA
has been investing its energy and resources in important
initiative such as the Current Good Manufacturing Practices for
the 21st century initiative, or the GMP initiative. Under that
initiative, FDA is working with industry to encourage the use
of advanced technologies, as well as quality systems and risk-
based approaches, that build quality into the manufacturing
process and avoid the problems such as those Chiron
experienced.
Thank you very much.
[The prepared statement of Mr. Crawford follows:]
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Chairman Tom Davis. Thank you very much.
Mr. Waxman and I have agreed to begin the questioning. We
will take 15 minutes and then Mr. Waxman will get 15 minutes on
his side, and then we will go down and allow individuals to get
their 5 minutes, should they desire to do so.
Dr. Crawford, let me start the questioning. FDA provided
the committee with the Form 483s from the June 2003 and the
October 2004 inspections of Chiron's Liverpool facility. This
is an important point because a lot of has been made about a
duty, perhaps, of the FDA to have gone back and continued to
inspect that plant prior to October 2004.
Could you explain the differences between these two forms
and why, even though some similarities exist between faults
that were found in the June 2003 inspection and October 2004
inspection, that Chiron's license suspension in October 2004
was not foreshadowed by the June 2003 inspection?
Mr. Crawford. Well, the two events were unrelated. In 2003
we inspected the plant and were involved with it, and we did
issue Form 483, which cites some corrections that must and
should be made; and the plant responded affirmatively. We were
able to interact with them in a productive way; and the proof
of that was that the 2003 vaccine production was completed on
schedule and none of it was condemned, as was the case in 2004.
So they are two entirely separate situations. The 2004
situation was quite different.
Chairman Tom Davis. When the team biologics returned to the
United States after its June 2003 inspection of Chiron's
Liverpool facility, it initially recommended that official
action be taken against the facility. FDA ultimately decided
that voluntary action should be taken. Can you explain to us
the protocol FDA follows in deciding actions after routine
inspections of manufacturing facilities?
Mr. Crawford. Yes. The inspectors that actually do the
evaluation onsite come back and make a recommendation as to
what kind of action FDA should take, if any, and then team
biologics actually has a decisionmaking process so that all of
the members of the team are able to evaluate the severity of
the situation and also what progress is being made. By that
time, they did have the response from the company to the 483,
and based on that, and also based on the fact that vaccine
production process last year did come to full and successful
completion, the action was changed from mandatory to voluntary.
Chairman Tom Davis. FDA's routine protocol, as I understand
it, is to inspect foreign manufacturers once every 2 years?
Mr. Crawford. That is correct.
Chairman Tom Davis. The last routine inspection of Chiron's
Liverpool facility, then, was June 2003. FDA informed the
committee it accepted Chiron's response plan to correct the
issues that were raised in June 2003 and, therefore, the file
was closed on September 3, 2003, is that correct?
Mr. Crawford. That is correct.
Chairman Tom Davis. If these steps were following standard
FDA protocol, would there be a reason for FDA to go back to
Chiron's Liverpool facilities prior to the 2-years time to
reinspect?
Mr. Crawford. No, we don't do that.
Chairman Tom Davis. So you were following protocol.
Mr. Crawford. Yes.
Chairman Tom Davis. Let me just ask you this. In
retrospect, now that we have seen what happened, is there
anything in inspection in that time period that might have
shown that we should have gone back? I know it wasn't within
protocol.
Mr. Crawford. No. Within the number of years that we have
been doing this, for decades, this has been our standard
protocol. It is modified somewhat from time to time in order to
deal with the good manufacturing practices, as practices within
the industry change, but the sequence of events has been
unchanged over recent years and has been very effective. This
is the first time we have had contamination in final lots of
vaccine at that plant, and that was a different kind of thing.
But we would not have changed the protocol leading up that.
Chairman Tom Davis. You believe that the causes of the
contamination in the vaccine in October 2004 were unrelated to
the initial reports that we got back in June 2003 and potential
contaminations at that point?
Mr. Crawford. Yes. The flu vaccine composition is changed
each year based on the expected strain, so this was an entirely
different production.
Chairman Tom Davis. Now, let me step ahead a little bit and
try to understand that everyone's goal this year, MHRA,
Chiron's, the FDA, is to get Chiron up and running so that they
can produce flu vaccine next year. They have gone ahead and
ordered the eggs; the invested financially in being able to go
ahead next year and get the doses up and the supply ready for
the United States.
But if Chiron isn't up and operating, if something goes
wrong, if the changes that they are making within their planned
operation somehow do not pass muster and we still have
contamination, can you tell the committee what is our Plan B?
Mr. Crawford. Well, at that point it will be early enough
for us to seek alternative production facilities, but also
alternative sources of vaccine from other countries and
elsewhere. So that will be a signal to both the British and to
us that we need to work with their version of the Centers for
Disease Control and our version of our own CDC in order to work
together to secure an adequate vaccine supply from other
sources, if in fact they are not going to be able to provide
it.
As you recall, we testified in 2002 that the vaccine
industry was extremely fragile; we would be down to a very few
suppliers, and we needed to work on that. When you find out too
late in the production season, it is too late to seek
alternative sources because they can't get up and running fast
enough. It will be earlier than that this year.
Chairman Tom Davis. You also have foreign license
manufacturers. In fact, Chiron has other plants, do they not,
where they manufacture vaccine?
Mr. Crawford. They do.
Chairman Tom Davis. Are we in the process of going out to
other manufacturers that are currently providing dosage for
Europe and for other parts of the free world, and have met
criteria in other countries, to get those licenses as well, so
that, should this occur again, we have other sources of supply?
Mr. Crawford. Yes. I have personally talked to every chief
executive officer manufacturing flu vaccine anywhere in the
world, even those that have elected not to come to the U.S.
market, and have encouraged them to do that and also have
encouraged them of the commitment of FDA to work with them in
that process, because we need more competition, if you will,
within the flu vaccine industry. I have also talked to the
manufacturers of substances like FluMist and also the antiviral
drugs, and have assured them also of our commitment. Some of
them, the antiviral drug manufacturers, also have chosen to not
enter the U.S. market. I have encouraged them to rethink that,
and we are having a continuing series of calls on a virtually
daily basis in order to see what their thinking is and also to
work with them.
Chairman Tom Davis. It is true that worldwide there is a
shortage of flu doses? It is just that in the more affluent
parts of the world we tend to be able to go out and buy it and
usually have ready supply? Is that a fair comment?
Mr. Crawford. Yes. Dr. Gerberding would be better able to
talk about that, but we consume more than our share of the flu
vaccine that is produced worldwide. That is as it should be; we
have a very aggressive public health program thanks to CDC, and
we are moving forward, I think, to vaccinate an even larger
percentage of our population. But the number of companies that
are actually manufacturing are down really to about three or
four.
Chairman Tom Davis. Dr. Gerberding, is that an accurate
statement?
Dr. Gerberding. That is accurate. I don't have the global
production figures this year--we can get them for the
committee--but in most years it is less than the total of 300
million doses globally.
Chairman Tom Davis. OK. What is the annual death toll from
influenza around the world? We know it averaged about 36,000 in
the United States in an annual basis. What would it be
worldwide, any idea?
Dr. Gerberding. We don't have accurate estimates globally
because there really is no system for surveillance for flu
deaths on an international basis.
Chairman Tom Davis. In many countries.
Dr. Gerberding. We are working on that, but I can't answer
the question.
Chairman Tom Davis. OK.
Let me go back to you, Dr. Crawford. What are Chiron's
obligations to FDA in order to get their license back to
produce Fluvirin vaccines for next year's flu season, and how
are you working with Chiron and the MHRA to develop and
implement the remediation plan, and how confident are you that
we are going to be successful?
Mr. Crawford. Thanks to an agreement that has been reached
between the MHRA, FDA, and Chiron, we are now able to share
information and also to work together in helping to get the
vaccine production facilities----
Chairman Tom Davis. And that is the first time we have had
that, correct?
Mr. Crawford. It is, yes.
Chairman Tom Davis. In fact, without that, under British
law, they couldn't share this with you.
Mr. Crawford. They could not and did not share information.
We are now working hand-in-glove to get that particular plant
up and functioning, and a decision will be made on that by
January 5. Now, it is important to note that since the facility
is in the United Kingdom, the license will come from the
British Government.
Chairman Tom Davis. Correct. And we have talked about the
Plan B, that at that time you still have time to look worldwide
into other areas.
Mr. Crawford. Yes.
Chairman Tom Davis. Let me ask you another thing. We have
some jurisdictions, State of Illinois, city of New York, that
are talking about importing vaccines from countries that are
not FDA certified.
Mr. Crawford. Yes.
Chairman Tom Davis. What are we doing about that?
Mr. Crawford. Some Governors and mayors have come to FDA
and have offered to go and try to find vaccine that is still
unused in wholesale distribution channels, and they have found,
starting with the Governor of Illinois and then the last one to
enter the situation was the mayor of New York City, they have
come up with up to 750,000 extra doses. And what we are doing
now is we had to first collect the lot numbers on those doses
in order to be sure that they were legitimate, that they came
from the plant where they were supposed to have come from. The
second this is now we are developing what is called a pedigree,
and that is to be sure that we know where all this vaccine has
traveled throughout the world and whether or not the cold
chain, as it is called, that is, refrigeration, has been in
place sufficiently and adequately to make sure that the vaccine
is still viable and can be used.
We are down to that point now, and we are also meeting with
that CEO on a regular basis as they help us to get the data we
need in order to bring the vaccine in. Now, it is not approved
in the United States, so we will have to do some special
procedures in order to bring it in, but we are not at that
point yet, but we are making progress.
Chairman Tom Davis. And I would just emphasize, from my
perspective, for next year and the years after, we just need to
get more providers out there. And if we can't get them to
produce it here, we have to go worldwide to just get them
certified, where they can do that.
Also the FluMist, are we looking at testing that to see if
that can have a wider applicability than it has?
Mr. Crawford. Well, as I mentioned, they are going up to 10
million doses, and as you also know, it is now used for people
that are in healthy physical condition between the ages of 5
and 49. The company has released information that they are
interested in perhaps expanding that perhaps to some further
ages, and I can assure you, although we can't reveal the
procedures and what is going on in terms of the data that has
been submitted to us and the relevant applications, we will do
everything we can to work with them or anyone else who wants to
expand a flu vaccine product in the U.S. market.
Chairman Tom Davis. OK.
Dr. Gerberding, let me ask you. Getting parochial,
Virginia, Maryland, and D.C., this whole region, we are all
heavily dependent on Chiron to supply our vaccines for the
public sector. How has the CDC worked with Aventis to
redistribute the portion of the Aventis flu zone doses to
States that contracted solely with Chiron?
Dr. Gerberding. On October 5th, 33 million doses of Aventis
vaccine had already been distributed, but there were a
projected 25 million doses left to be allocated. The first
phase of allocation was targeted to people who need the vaccine
the most. So looking at the Aventis purchasers, as well as the
public sector purchases, we did everything we could to ensure
that we got all the doses out to the Vaccine for Children
Program, doses going to nursing home and to other high-priority
obvious areas where there were most likely to be people who
needed it.
Once that plan was developed and implemented, then the
remaining 12 million or so doses needed to be allocated, and in
this step the State health officials stepped in and said we
will work with CDC and Aventis to target those doses of vaccine
to the places in our communities that need vaccine the most.
Thus the States have really done an assessment of where it is
needed, how it is needed, and we have made sure it has gotten
there.
In this process of working with the States to allocate the
vaccine, we have made available to them, for the first time
ever, proprietary information on a secure Web base that tells
them now just how many doses, but exactly to whom Aventis
shipped the doses. The Chiron distributes have been providing
that information now as well. Therefore the doses are going, at
the direction of the State health officials, to the people in
those jurisdictions who need them the most.
Chairman Tom Davis. Let me ask. If you go back to October,
it looked like we had about 50 million doses nationally
available, is that about right?
Dr. Gerberding. In October we had already used 33 million
of the----
Chairman Tom Davis. I am talking about total doses
available. With Chiron not being able to produce it, we were
going to be around 50 million doses. Is that right?
Dr. Gerberding. A total of 61 million doses total this
year, including 3 million doses of the FluMist.
Chairman Tom Davis. But part of that is because we have
stepped up efforts since October, isn't that correct?
Dr. Gerberding. Right. Exactly.
Chairman Tom Davis. I am just saying it was about----
Dr. Gerberding. Aventis had a higher than expected yield,
and they were also able to get a few million more doses out of
the production line.
Chairman Tom Davis. So we are up to 61? Will that go any
higher, do you think, looking at some of the foreign
distribution?
Dr. Crawford, do you know?
Mr. Crawford. Yes.
Chairman Tom Davis. We were at 75 million doses last year.
What do we expect to be at the end of the flu season? How many
doses can we reasonably expect to have on the street, available
to the public? Anybody want to take a stab at that?
Mr. Crawford. Yes. We have made contacts with a variety of
companies, and we are in final negotiations with three of them
that are in other countries, and it is possible that we will
have an additional 5 or 6 million doses cleared for shipment to
the United States by the first of the year. The exact figure we
don't know at this point because we are continuing to
negotiate, but we have sent inspectors to those plants and they
have filed their findings. And I expect to have on the first
plant, which is actually the largest one, a recommendation by
the end of this week, and then I can make a determination as to
whether or not it meets U.S. standards and can be brought in
under special circumstances.
Chairman Tom Davis. You would agree, though, we need more
suppliers to avert this kind of thing in the future? Does
everybody agree with that?
Dr. Gerberding. Absolutely.
Mr. Crawford. Yes.
Chairman Tom Davis. And that means the FDA is going to have
to be proactive in going out and getting some of these other
areas licensed, is a fair assumption?
Mr. Crawford. It does. Yes.
Chairman Tom Davis. Dr. Gerberding, let me just conclude.
What lessons from our response to this year's flu vaccine
shortage are really relevant to bioterrorism preparedness?
Dr. Gerberding. Well, the systems that we have been using
to track and allocate flu this year are the same systems that
we would use for a pandemic or for a terrorism event. I think
it has been a challenging exercise. We have been asking a lot
of our public health system in this regard, but the laboratory
network, the communication network, the emergency operations
network, and really the countermeasure allocation system that
we have executed are all critical components of any emerging
threat, including terrorism.
Chairman Tom Davis. And they are working pretty well under
these circumstances?
Dr. Gerberding. Well, so far we have been very pleased with
the steps that have been taken and the success that we have
had, but, again, it is early in the season and we have a long
way to go before we are through with this.
Chairman Tom Davis. Thank you very much.
Mr. Waxman, you have 15 minutes.
Mr. Waxman. Thank you, Mr. Chairman.
Dr. Crawford, I want to start my questions with you. In
1999 the Food and Drug Administration inspectors went to a
Liverpool plant and they identified manufacturing problems--
this was before Chiron purchased it--and the inspectors
responded to these problems by issuing a warning letter. And as
I understand the significance of a warning letter, it is an
official enforcement action. If the manufacturer doesn't
correct the problems or remedy the violations, FDA can initiate
legal action against them. So it is a serious matter. And, in
addition, once there is a warning letter, it generally ensures
that another inspection will be conducted to make sure the
problems have in fact been fixed. So that is what happened in
1999.
In June 2003 FDA inspectors went out again. There were four
inspectors, as I understand it, to look at this Chiron plant in
Liverpool. And they found bacterial contamination, in some
cases 1,000 times higher than expected. They found unsanitary
practices. They found the plant was not doing an adequate job
investigating and correcting these problems. The June 2003
inspection team recommended, as I understand it, unanimously
that there be an official action, as there was in 1999. Instead
of a warning letter being sent, which would be official
actions, the recommendation was ``downgraded to a request for
voluntary action by the company,'' a request that carries no
legal weight and that did not lead to a prompt followup
inspection.
What I am concerned about is why did FDA downgrade its
response and ask for only a voluntary action?
Mr. Crawford. It is because of the progress that the plant
was making. We issued what is called a 483, which is a
statement of what we think should be corrected. We stayed in
touch with the plant as they moved toward the end of that
production cycle. Two things happened: they responded very
well, they corrected the problems; and then the vaccine
production in that plant for that year, which was ready for our
evaluation a few weeks later, turned out to be OK. The 2003
production was not contaminated. So they had in fact completed
what we wanted them to do and there was no need to have
mandatory or a warning letter.
Mr. Waxman. Well, there was no need, but there could have
been, and that would have enforced another inspection. In fact,
did FDA go back to the plant to inspect whether conditions in
the plant were actually improving as you thought they were or
you hoped they were? Did you schedule another inspection, as
FDA would likely have done if you had taken an official
enforcement action?
Mr. Crawford. Well, two things happened, as I mentioned.
Mr. Waxman. Well, could you answer yes or no on that
question?
Mr. Crawford. Pardon me?
Mr. Waxman. Could you answer yes or no?
Mr. Crawford. Would you restate the question?
Mr. Waxman. Well, you didn't send an official letter, which
would require followup inspection; and you thought things were
improving. And I want to know did FDA go back to the plant and
inspect whether the conditions in the plant were actually
improving, as you hoped they were, and did you schedule another
inspection, as FDA would have done had you issued an official
letter?
Mr. Crawford. Well, it is not possible to answer that yes
or no because we did go back in August 2004. If that is the
question, the answer is yes.
Mr. Waxman. Well, the answer wouldn't be yes, because under
an official letter you would have gone back earlier than that.
Mr. Crawford. But they corrected the problems.
Mr. Waxman. Well, how do you know they corrected the
problems?
Mr. Crawford. Because we got the vaccine produced and it
was OK.
Mr. Waxman. That was the final product.
Mr. Crawford. In 2003.
Mr. Waxman. But in the 2003 inspection your people said
that there were unsanitary conditions there, that there is a
high bacterial contamination. Maybe it wasn't in the final
product that you saw, but it certainly became the reason why
the British shut down the plant in 2004, isn't that correct?
Mr. Crawford. No, that is not correct.
Mr. Waxman. It is not correct? OK, we will get to that in a
minute.
I think it was a mistake for you not to have gone back
earlier than 2004. If you had issued an official letter, you
would have had to have gone back earlier. And the reason it was
a mistake is conditions weren't getting better, as you thought
they were; they were deteriorating. But because you weren't
there in the plant until 2004, when we already had a problem
that was much worse, you had no idea how bad things actually
were. Unfortunately, what happened at the Chiron plant I think
is emblematic of larger problems at your agency, but let me get
to that in a minute as well.
FDA inspected the flu vaccine supply in June 2003. The
report of the inspectors found serious problems in 20 areas of
vaccine manufacturing and distributing. You stated that FDA's
oversight in 2003 had no relevancy for 2004. I want to ask you
first about the finding of high bio burden, meaning high levels
of bacteria in the vaccine production process. In 2003 FDA
found evidence of bio burden more than 1,000 times higher than
expected, even after they had this filtration system to stop
it. FDA also found that on repeated occasions the vaccine pools
had been contaminated with potentially lethal bacterial called
serratia; and FDA even found contamination in the vaccine after
sterile filtration, which is supposed to eliminate any
potential for bacterial growth.
Now, is it not true that if these findings of high bio
burden, how you can say they had no relevancy, the problem that
led to the closure of the plant in 2004?
Mr. Crawford. Well, as you mentioned earlier, in 1999 we
had this same sort of problem with the bio burden. As you know,
every vaccine production lot starts off with a bio burden, and
production is in large place decontaminating it so that it goes
back to a sterile situation. After 1999 we had a perfectly fine
production in 2000; after the findings of 2003, that vaccine
turned out to be OK. There was no linkage between it and what
happened in 2004.
Mr. Waxman. Well, in the documents that we finally got from
you--and it took a while to get it--this was the inspection in
2004. They talked about this high bio burden in the lots and
they said ``not corrected from previous inspections in 2003, in
that similar occurrences noted during this inspection.'' So
when they went back in 2004, the FDA inspectors found the same
problems they found in 2003, a high level of bacteria that can
contaminate the supply. And I think this is a key point. In
2003 FDA found problems at the company investigating sterility
failure, and it was the failure at the plant to investigate and
correct the 2004 contamination that led to the shutdown.
Mr. Crawford. No, that is not correct.
Mr. Waxman. What led to the----
Mr. Crawford. Bio burden is present in every production lot
of flu vaccine; it starts with a bio burden and then the point
is that the bio burden has to be reduced and eliminated.
Mr. Waxman. They had problems with the bio burden; it was
1,000 times more than it was supposed to have been. Is that
right?
Mr. Crawford. What year are you talking about?
Mr. Waxman. 2003.
Mr. Crawford. They had problems, but they were able to
decontaminate it, so the vaccine actually went on the market.
Mr. Waxman. Well, your inspectors went back in 2004, and
they said the problem had not been corrected for the bio
burden. When you finally went back on October 15, 2004, you
found a high bio burden that hadn't been adequately
investigated. And this inspection expressly stated it wasn't
corrected from the previous inspection in 2003. When you read
these documents, it is clear that the bio burden problems and
Chiron's failure to be able to identify and correct them were a
significant factor behind the closure of the facility. They
existed in 2003, they weren't corrected; they got worse in
2004. As I mentioned, the FDA inspectors, in 2003, found
evidence of contamination in the vaccine, even after sterile
filtration that is supposed to remove all bacteria, ``a
potential source of contamination was identified in the aseptic
connections between the tanks of the vaccine and the
formulation area.''
So in June 2003 FDA found that the company had failed to
address these problems with these connectors, and this year
Chiron investigated its most recent contamination problems and
the company found a major weakness and possible cause of the
contamination in the aseptic connections. FDA scientists wrote,
``The contamination most likely occurred during the multiple
number of aseptic connections in the formulation stage.''
So let me ask you this question. Aseptic connections were
identified as a potential source of contamination in 2003. They
weren't fixed. They then were identified by both Chiron and FDA
officials as a likely source of contamination in 2004. Doesn't
that make the 2003 inspection and FDA's failure to followup to
make sure the problems were fixed relevant to the problems in
2004?
Mr. Crawford. No. The bio burden comes in with the eggs,
the chicken eggs that the virus is grown in, and it is discreet
to that particular year. The bio burden of 2003 is long gone.
So you bring in a new bio burden with the new chicken eggs, and
what you have to do is reduce that load through various means.
Mr. Waxman. Your staff met with our staff this week, and
when they met, your senior FDA officials conceded that a number
of findings in 2003 were relevant to the 2004 problems. These
included problems not only with the bio burden and the aseptic
connections, but also with the basic sanitary practices in the
facility. In essence, what they told us is that the problems
identified in 2003 didn't get better, as FDA hoped they would;
instead, as production volumes increased in 2004, the problems
at the plant expanded, ultimately leading to the shut down of
the facility.
I would submit that this was a serious cost of the FDA
failure to be more vigilant. If the agency had taken official
enforcement action, as the FDA inspectors asked for, as they
recommended, the problems at the plant might have been
corrected and the flu vaccine crisis might have been averted.
And if FDA would be more honest about what happened and the
mistakes that were made, the public would have greater
confidence that the agency will correct its mistakes and can be
trusted in the future.
Dr. Crawford, I know you want to say this is different, but
essentially what we have is a plant that has had troubled
sanitary conditions in its production, and those troubled
sanitary conditions eventually led to the contamination of the
vaccine supply. That is what caused the shutdown by the
British. That is what your FDA people saw when they finally got
out there. I would submit to you that now that we have these
documents, it is not good enough to say, well, things were
getting better. They weren't getting better; the problems
hadn't been corrected; the production was being increased. And
with the increase in production and the facilities not having
their sanitary problems corrected, we ended up with a
breakdown.
Mr. Crawford. Well, I had to condemn, as you know, the
production for this year based on the fact that the bio burden
could not be reduced this year; and that didn't happen in 2003.
It was one of the toughest decisions I ever had to make, but we
could not allow that vaccine into the United States. We had to
take that particular step, and we are working now with the
British to see what can be done for the next flu season.
Mr. Waxman. Well, you say it was a very tough decision for
you to make, but in fact it wasn't you that made it, it was the
British who shut down the facility and prohibited Chiron from
selling any vaccine.
Mr. Crawford. No, we already had between 6 and 7 million
doses in the United States. We sent a team over to do an
inspection of the plant, and then I had to make the decision.
That is the sequence of events.
Mr. Waxman. That was after the British action or before the
British action?
Mr. Crawford. That was when the British notified that they
were suspending the license. We already had the vaccine here in
the United States.
Mr. Waxman. Well, the point is clear: the British suspended
the license because these problems were contaminating the
vaccine supply. You had some of the supply here; you decided
you can't use that supply. The British had already shut down
the plant.
You said that there was no relevancy to the June 2003
inspection to later problems. I just dispute that statement.
You said that the FDA assured that Chiron took all steps to
resolve the problems from 2003. But FDA had not done any
reinspection of the facility, and your own inspectors found
this to be untrue in October of this year, finding that a key
issue involving contamination was not corrected since the
previous inspection.
All of these statements that I think were made by you and
others in the administration that were not accurate had the
effect of reassuring Americans, before the election, about the
Bush administration's role in the flu vaccine shortage. Prior
to the election, FDA withheld documents from this committee
that revealed the truth. FDA ostensibly said that there was a
reason to not send us the documents at the time we requested,
because the individuals who were to produce the documents were
too busy trying to find more vaccine. But when we look at the
fax cover sheets now with these documents, they were sent to
you by individuals on October 18th, 2 days prior to our
deadline, just as I had been informed by an FDA employee.
So what I am picking up here is a pattern of misleading
statements, and maybe even political calculations, that I think
reflect poorly on the administration, but I think they do an
enormous amount of damage to the credibility of the FDA.
I did want to get into the other enforcement actions that
have not been followed through by FDA. We have seen just
dramatic decreases in enforcing the law. I know you consider
this a routine procedure, but this is not a routine procedure
when you are talking about half the vaccine supply of the
United States.
Mr. Crawford. Can I respond to some of this?
Mr. Waxman. Please.
Mr. Crawford. Every statement I made was accurate. As you
know, the chairman granted us an extension of time so we could
produce the documents that were requested all together, and not
just dribble them in. So we complied with the chairman's
timing.
Mr. Waxman. I just want to ask this one last question,
because my time has expired. How could you say there was no
relevance for the inspection in 2003, when your inspection in
2004 had specifically noted on it by the inspectors that the
previous problems had not been corrected from 2003, which have
to do with contamination of the facility?
Mr. Crawford. The problems were corrected, because the
vaccine production was good and could be used. They use the
same terms, and that may be where the confusion is coming in.
Mr. Waxman. Your inspectors said that wasn't true, though.
Mr. Crawford. Because if something happened like in 1999--
--
Mr. Waxman. So you think the problem was----
Chairman Tom Davis. The gentleman's time has expired.
Mr. Crawford, I want to give you an opportunity, if you
want, to finish that.
Mr. Crawford. No, I was just saying they used the same
terms of art to describe inspections, you know, maybe over a 20
year period. That doesn't mean that whatever it is, like the
bio burden doesn't occur from year to year----
Chairman Tom Davis. Well, let me ask. You could have taken
the 1999 inspection and said that had a problem with 2004 as
well, couldn't you, under the same logic?
Mr. Crawford. Absolutely.
Mr. Waxman. Would the gentleman yield just on that point?
We are not talking about something years before, we are
talking about 1 year earlier they told you there was a problem.
You said it didn't show up, so it was corrected, but it didn't
appear to be corrected according to your own inspectors.
Chairman Tom Davis. I think he just explained it.
Mr. Waxman. If it hadn't been corrected, I think that's a
problem----
Mr. Crawford. I have already answered that. They were
corrected.
Chairman Tom Davis. I think he explained it, and I don't
think we are going to reach a closure on this.
Mr. Mica, you are recognized for 5 minutes, and then we
will go, Mr. Waxman, to you.
Mr. Mica. Dr. Crawford, don't you realize how many times
you deny the accusation, that it is still thrown at you? Dr.
Crawford, this little exhibit here, warning letters for
biological manufacturing violations have dropped sharply since
the fall of 2001. Actually, it goes back to 2000. Are vaccines
considered part of biological manufacturing?
Mr. Crawford. Yes, they are.
Mr. Mica. And hasn't there been a significant drop in
actual manufacturers of vaccine?
Mr. Crawford. Yes. We are down to only----
Mr. Mica. So if we have fewer people producing the
vaccines, then we would have fewer people to go after.
This is a great example of trying to now blame the
bureaucrats, as I have said, and FDA. Now, FDA, you don't know
it, but you are the fall guy. I have sat on this panel now for
12 years, and I have been through vaccine hearings over that
period of time, and first the folks on the other side, they
blame the drug manufacturers; these are bad people and they
were producing bad stuff, and they were charging too much for
it. So then the next routine was it is not just the drug
manufacturers, it is those bad insurance companies, because the
cost went up dramatically. And I think I cited at the last
hearing one vial someone held up and said this only costs $1 or
$2, the actual vaccine itself, but the insurance costs $20 or
$30, if you could get it.
Now we have no manufacturers in the United States, I guess
except for nasal vaccines. We have no insurers, so it is your
turn to be the fall guy, and it is your fault. Don't you
understand that? Now, you just heard that if you had gotten
there a little bit earlier or sent a warning a little bit
earlier, there wouldn't be any shortage. Is that correct?
Mr. Crawford. I did hear that.
Mr. Mica. Well, first we go on the premise that you weren't
there in time, which you have said you acted in an appropriate
manner. But somehow even if you had acted a few weeks earlier,
would we have a flu vaccine shortage today?
Mr. Crawford. It wouldn't have had any effect, because it
started just in January.
Mr. Mica. And you have made that point. But the root
problem and cause, and a lot of folks in Congress don't want to
admit it, are, first of all, liability. It is kind of
interesting that you had trouble getting to Liverpool to look
at a manufacturer.
I submit for the record this article from the International
Herald Tribune that shows France, Germany, and Switzerland, for
example, followed the so-called British rule, where the losing
party pays the cost of winner's lawyer, and it goes on to
describe how difficult it is in the countries where they are
manufacturing flu vaccine, where you have to fly over and try
to find out what they are doing, how much easier it is to
produce that and how much more difficult it is to sue and have
lawsuits, which have driven manufacturing out of the United
States.
Chairman Tom Davis. Would the gentleman ask that article be
put in the record?
Mr. Mica. Oh, yes. I am sorry.
Chairman Tom Davis. Without objection, the article will be
entered into the record.
[The information referred to follows:]
[GRAPHIC] [TIFF OMITTED] T7448.179
[GRAPHIC] [TIFF OMITTED] T7448.180
Mr. Mica. So, one, we need liability and tort reform. Until
we get that, folks, you are not going to have health care cost
reduced. It is interesting. Pick up the papers today and see
how, in a couple of the papers, how many more doctors are
closing down their operations, how many health care providers
are going out of business or relocating their activities. And
that will continue until you get some tort and liability reform
in medicine.
Regulatory reform, and it now takes some 8 months, and you
have described the process.
Let me go back first. The accusation is maybe we haven't
spent enough money, because you have to always spend a lot of
money.
NIH, that is Dr. Fauci. In 2001, on research, we had a 10
percent increase from 2001 to 2002. I am not very good at math,
but that is what it looks like. Even before all this came out,
I don't want to say we doubled, we went from 22.8 to 57.4,
which I would say is about 160 percent increase in research. So
that goes out the window.
Chairman Tom Davis. Does the gentleman have a question? His
time has expired.
Mr. Mica. OK.
Chairman Tom Davis. Mr. Waxman, you are recognized.
Mr. Mica. Well, I have a number of points and a number of
questions. I am willing to stay for a second round, but I am
trying to get at the root problem and identify liability,
regulatory reform, and I have a host of questions about the
States buying this, about guaranteed purchases by the
government that have driven up costs. And I will get to those
when I have adequate time. Thank you.
Chairman Tom Davis. Thank you.
Mr. Waxman, you are recognized for 5 minutes.
Mr. Waxman. Mr. Chairman, my colleague, Mr. Mica, didn't
get to his questions because he was making absolutely incorrect
statements about a lot of different things. He used the
opportunity to say we have all, on this side of the isle,
accused the manufacturers of being bad people. We have never
said that. He is saying it is terrible we are accusing the FDA
bureaucrats of maybe not doing the right thing. He doesn't
believe that. He thinks it is malpractice or liability issues
that has caused the problem we face today.
Well, I would submit that it was not the liability laws
that caused the contamination of vaccine in Liverpool. It was
the fact that they had unsanitary conditions there. And the
inspectors from Britain found that out to be the case, and
eventually our own FDA came to conclude that was the case. And
I don't consider Dr. Crawford or the FDA to be bad people, but
my criticism is that the FDA didn't do enough to stay on top of
this issue. They knew from previous inspections in the year
before, 2003, that there were problems at that plant, and they
never went back for another inspection, until after the British
closed the plant down.
I disagree with Dr. Crawford's statement that it was
irrelevant that they found that there was contamination in
2003. He said there was contamination in 2003, but that wasn't
the problem in 2004. His inspectors said that was the problem
in 2004 because it hadn't been corrected in 2003. Well, if you
take Dr. Crawford's statement, it would have to be they
corrected it and then they went back into a contaminated state.
That doesn't follow.
Now, let me just address the liability issue, because that
is really a red herring. The gentleman speaks with a great deal
of ignorance, because in the liability area vaccines were a
problem; manufacturers weren't making any vaccines for fear of
liability. And I authored, and the Congress passed, the vaccine
compensation system. It has been very successful by providing a
fund to compensate those people who are injured from a
vaccination. It has been very successful in keeping people from
going to the courts.
The flu vaccine is part of that vaccination system. None of
the drug companies, none of the advisory committees to the FDA
have come in and said we ought to change the immunization
problem, liability for immunization, because it is not a
problem in this case. I will leave to another time to discuss
the problems of medical malpractice, which I do think is a
serious problem causing higher prices in the practice of
medicine.
I just think it is important, especially if this is on C-
SPAN--I don't know if it is or not, but following his
statements made with such abandon and such ignorance, I think
somebody should correct the record.
I do want to take advantage of the fact that I have my 5
minutes, and I thank my colleagues for indulging me to do this.
But FDA has, I think, undergone a very serious change in
direction in the way they have been responding to a number of
the problems not just in this area, but this area is emblematic
of it.
Well, we have a chart over there, it is the ``Warning
Letters for Biological Manufacturing Violations.'' They have
dropped sharply since the fall of 2001. You can see in 1997
there were 17; in 1998, 19; and then after 2001 there was 1, 2,
and 1. A big drop. We have seen the warning letters to
manufacturers who are making false and misleading statements in
their advertising. They have dropped dramatically. I would
submit that FDA is just not enforcing the law. I was concerned
that they just didn't even enforce the food labeling laws,
which I also had a part in authoring.
Dr. Crawford, why do you think that is happening at FDA?
Why is there a precipitous drop of enforcement actions?
Mr. Crawford. Well, there are not as many people to
regulate, not as many companies, as was stated earlier. But we
have not lessened our profile in terms of evaluating these
companies. But there is variability. If you take it back a long
period of time, you will see that some years it is up, some
years it is down.
Mr. Waxman. Well, we see a dramatic----
Mr. Crawford. But if we still had 20 manufacturers, it
would be up higher.
Mr. Waxman. Well, I am not talking about just vaccines. But
even for the false and misleading statement by all
pharmaceutical companies in their advertising, an 80 percent
drop in any kind of enforcement actions to be sure the public
is not mislead.
Mr. Crawford. Well, we do have fewer drugs that are on the
market that have prescription status and are still in patent,
also, so that would account for it. But we have not lessened
our attention to this kind of activity.
Chairman Tom Davis. Thank you.
The gentleman's time has expired.
Mr. Deal, you are recognized for 5 minutes.
Mr. Deal. Thank you, Mr. Chairman.
Dr. Gerberding, thank you for being here. We appreciate the
fact that you and the CDC in my State of Georgia are doing such
a good job.
I would like to ask you just briefly you have outlined what
you have done in this rather critical situation of a shortage
of the flu vaccine in terms of trying to make sure that what is
available is delivered to the most critical places. What role,
if any, would the CDC play in a normal situation? Do you
participate in those decisions in the absence of a shortage?
Dr. Gerberding. Unlike childhood vaccines, the flu vaccine
market is almost entirely in the private sector, so CDC only
purchases a very small amount of the vaccine. Therefore, we
have only a limited capacity to target or direct our supply to
the appropriate individuals. In the last 5 years of vaccine
production, every year vaccine doses have gone unused. So, in
general, the private sector distribution has targeted to the
people who are willing to take vaccine. This year, of course,
we are expecting the profile to be very different.
What we do is work with our expert advisory committee, the
ACIP, to make the recommendations, the science-based
recommendations about who will benefit from vaccine and how
they should be vaccinated and when they should be vaccinated;
and then the adult immunization mechanisms in the health care
delivery system and in the public sector at the State and local
level kick in to actually administer it.
This is one of the things that we are looking at, is
opportunities to improve our typical coverage of this vaccine,
which has never been ideal. We would like to have a higher
demand for flu vaccine and we would like to assure that
everybody who needs a dose gets it.
Mr. Deal. You mentioned something about the fact that it is
fragile. What is the shelf life of the injectable vaccine? I
assume it can't be frozen and preserved in that fashion. What
is the shelf life for a vaccine?
Dr. Gerberding. With this particular vaccine, the shelf
life, assuming that the cold storage is maintained properly, is
not very relevant because the virus changes every year. So the
shelf life is longer than a year, but it doesn't help us very
much because we need to make a brand new vaccine every single
year; and that is part of the challenge that this particular
infectious disease presents to us. That is part of why Dr.
Fauci's comments about the need for modernizing the vaccine is
so very critical. Imagine if we didn't have to get a flu shot
every year. We would be in a very different situation than we
are right now.
Mr. Deal. There are obviously disagreements and opinions as
to why we have so few manufacturers. Am I correct that one of
the earlier statements, that there is no domestic U.S.
manufacturer of an injectable vaccine for the flu? Is that
correct, there is no American domestic producer?
Dr. Gerberding. Aventis is producing vaccine in America,
but their headquarters are in France. So the actual
manufacturing does occur in the United States for the product
that we are using.
Mr. Deal. How long have we been in a situation of having
only two major suppliers? How many years has that situation
existed?
Dr. Gerberding. Ten years ago we had five suppliers, and
there has been a gradual attrition over that period of time
until just the two injectable suppliers this year.
Mr. Deal. You know, you would think normally the old adage
of supply and demand would work in this environment. Obviously,
the normal forces are not at work here. And I would assume that
there are some truths to the allegations that the issues of
liability play a factor in the fact that we have so few
manufacturers available.
Is it simply not a profitable business? And perhaps the
second panel is more appropriate, perhaps, to ask that, and we
will try to ask it there. But from your perspective, is it the
lack of profitability that is limiting the supply?
Dr. Gerberding. We have a few big problems. One is that we
don't have a guaranteed market for the vaccine, and we have
unpredictable demand. The second is the manufacturers need a
fair price for the product that they are manufacturing; they
need to have a business case. The third issue is that making
this vaccine is risky, as Chiron discovered this year. This is
a very difficult manufacturing process; you start out with a
bio burden, and by the end you are supposed to end up with a
product that is sterile enough for use, and it is fraught with
opportunities for things to go wrong. While liability has
played a role, this is the first year that we have recommended
flu vaccine for children, which makes it eligible for the
vaccine injury compensation program. In past years, because we
hadn't recommended it for children, it was not on the list for
liability protection. And even that doesn't completely remove
all of the concerns about liability, it only covers the things
that are in the table.
So it is a complicated set of problems, and the bottom line
is the manufacturers need to know that they can make a strong
business case for producing this vaccine.
Mr. Deal. Thank you, Mr. Chairman.
Chairman Tom Davis. The gentleman's time has expired. Thank
you.
Mr. Van Hollen, you are recognized for 5 minutes.
Mr. Van Hollen. Thank you, Mr. Chairman, and thank you for
holding another hearing on this important issue. I want to
thank all the witnesses as well.
My first question is obviously this year we have to make
the best of the situation that we have before us, and we have
to relocate the existing vaccine to those people who are most
vulnerable. My question is what is the administration's plan,
if any, to prevent this kind of shortage from happening next
year and into the future? That is one question.
The second set of questions relates to the issues that Dr.
Fauci mentioned, with respect to the avian flu and the
pandemic, which is something obviously we need to be preparing
ourselves for not just as a Nation, but as an international
community. And my questions there are, No. 1, to what extent do
we have cooperation from many of the Asian countries, where
this flu is originating, that allows us to detect it early
enough to prevent it from spiraling out of control, to the
point where we can't isolate it and it becomes a pandemic? And
what recommendations, if any, do you have to make sure that we
have an early warning system in place, on the ground? I know a
number of people at CDC have been working on this and have been
frustrated by their lack, for example, of cooperation from the
Chinese. So that is one set of issues, the early detection.
The second set of issues relate to a vaccine, and whether
or not we are moving ahead as quickly as possible in coming up
with a vaccine; whether mutations in the avian influenza would
defeat the work that we are doing; and even assuming that we
are on the right track with respect to manufacturing a vaccine,
what are we doing in terms of the production capability,
because we haven't prepared adequately to have a supply of flu
vaccine where we know we have certain strains of flu, and at
what time would we be prepared from the vaccine production
point of view to confront an avian influenza pandemic?
I know that is a lot of questions, but these are obviously
big issues.
Dr. Gerberding. I will start, and then we will start the
baton down the table.
In terms of the scenario planning, worst case scenario
planning for next year, our Team B is working on this from a
CDC perspective, and the Secretary has also called a special
task force at the Department to really dig in to what can we do
now and what can we do soon to obviate this situation.
One major thing is to work with the existing manufacturers
to see what can be done to support the largest possible
production. And Dr. Crawford has already mentioned that Aventis
and MedImmune are looking at ways that they can increase their
production next year. Getting Chiron back online is clearly a
high priority for everyone. We may have vaccine available from
international manufacturers on an IND, an investigational drug
status, and that can allow us to get more doses in, and we are
working out the mechanisms for that as we speak. And also we
will certainly focus on prioritization early in the season and
make sure that we get the targeting when the first dose of
vaccine is available, not waiting until more than half of it
has been distributed, as we did this year.
So there are some short-term things we can do, but we
really look forward to working with the administration and with
Congress to figure out if there are additional incentives to
help expand the market and get the production up to where we
need it to be.
Dr. Fauci. Let me just extend that, Mr. Van Hollen, and
talk about what we are actually doing right now in preparation
for pandemic flu; and I alluded to it in my opening statement,
but let me just summarize it briefly for you.
We know now that there are a couple of circulating avian
influenza viruses. The one that is causing us the most concern
is H5N1. Another is H9N2, H7N7, a few others over the years.
But let us just focus, for the purpose of an example, on H5N1.
What we are doing now is we are assuming--and it may not be
correct, but the assumption I think is an appropriate thing to
do, because it will set into motion the machinery that will
prepare us if we have to switch in midstream. So we are
assuming that the H5N1 is something that we need to worry
about, so we are developing two things in parallel. The first
are pilot lots. We have isolated it by that rapid method of
reverse genetics, and we are in the process of making pilot
lots in small amounts, 8,000 to 10,000, from two companies; and
we are doing that in order to put them into the clinical trial
to determine things: one, is it safe, because we have not
vaccinated people with H5N1; we assume it will be because the
methodologies essentially stay the same; and, second, how much
do you need to inject to get an adequate immune response, is it
going to be one dose, two doses, or more?
In parallel, in the assumption that we will have an H5N1
problem, we have contracted with Aventis-Pasteur to get us 2
million commercial lot doses; and that is critically important
because the process that gets you the 8,000 to 10,000 doses is
not something that you can scale up to 10, 20, 30, 40 million,
but the 2 million of the commercial lot doses will set the
process in motion that if indeed we do need to scale up, it is
much easier to scale up.
Now, on the scenario that perhaps the virus will change so
much that the vaccine that we are making is not specifically
going to target that virus that now is spreading efficiently
human-to-human, the very process of scaling up with an avian
virus vaccine is going to put us in good stead to go and meet
that challenge.
So we are already doing it now.
Mr. Shays [presiding]. The gentleman's time has expired.
Your mic is not on.
Mr. Van Hollen. The issue of international cooperation. I
know it was a big question and a lot to cover.
Mr. Shays. If there could be a quick answer, I would be
happy to entertain it, but not a long one.
Dr. Gerberding. I can give you a quick answer.
We have a system called the global detection network, and
we are investing in laboratories around the world and scaling
up our ability to get those isolates and get them to CDC for
sequencing and onto the seed vaccine development process. We
are also sequencing all strains that are coming in.
Mr. Shays. Technically, I am next in line, but I notice we
have a number of colleagues in the democratic side of the isle,
so I will defer my questions and go to you, Ms. Norton. I think
you are next.
Ms. Norton. Thank you very much, Mr. Shays.
Two questions. One has to do with the kinds of issues local
jurisdictions are going through now to think of what they can
do now. I asked the District of Columbia Department of Public
Health to use its authority to issue its own regulations in an
effort to avoid panic and because, as you know, most of the
vaccine is in private hands and does not go to public health
authorities. They did so. As you know, every State in the
United States--this would also be the case in most cities--has
the authority, that you apparently don't have, to proceed on
its own to avoid a public health crisis. I want to know if you
have asked public health authorities to use their own local
authority to issue such regulations as they deem suitable, to
advise them that would be an appropriate thing to do in light
of what you know about our supply and the delays that are
already being experienced by local jurisdictions getting
whatever supply is available.
Have you asked those who do have authority to use their
authority? For example, a private physician who has regular
patients may well be under some very special pressure to give
the vaccine to people who are not in high-priority groups. It
would be much easier for that physician to say regulations
indicate I can't do it then to say that the CDC, who has no
authority over me, said I can't do it. So I want to know, since
you didn't have the authority, since you left us all out here,
whether you have at least asked local public health authorities
who do have the authority to use their authority.
Dr. Gerberding. We have indeed recognized the statutory
authority of the State health officers, as well as the local
health officials, to make decisions to protect the health of
people in their jurisdiction, and that is exactly why we have
been able to provide them with the detailed information about
their high-risk populations and the vaccines that are there.
Ms. Norton. I am sorry, I didn't get the answer to my
question. Has the CDC specifically advised local authorities
that it might be beneficial--not saying that you should do it,
but that it might be beneficial--for them to use their own
local authority to handle this public health crisis?
Dr. Gerberding. Yes.
Ms. Norton. Would you indicate to me whether that has been
in a written directive? Could I get a copy of it? How was that
advice given? What have you advised them to do specifically?
Dr. Gerberding. The State health officials have worked with
CDC to develop the criteria for vaccine allocation; they are
receiving the----
Ms. Norton. See, you are not answering my question, and I
have another question.
Dr. Gerberding. I am sorry.
Ms. Norton. I know you have been working with them to
develop the criteria. I have asked you something else; it has
to do with their legal authority to issue their own regulations
so that people know that you are not supposed to give these
doses outside of the priority groups. Now, I am not talking
about developing and whatever, I am saying very directly have
you said you have authority? We are not sure what you would
want to do with that authority, but when you have a public
health crisis, you should at least consider using that
authority if you think that authority would help alleviate the
crisis. I have given you the kind of circumstance I am talking
about, and I am asking a direct question and I want a yes or no
answer.
Dr. Gerberding. Yes.
Ms. Norton. Or if not a no--and if a yes answer, then my
followup question was what did you say? Give me a copy of it. I
don't know that my authority has received anything; at least
they have not reported any such thing to me.
Dr. Gerberding. We would be happy to provide you that
information.
Ms. Norton. Well, what did you say? I am asking you a
question here.
Dr. Gerberding. We said we encourage you to exercise your
statutory authority to make decisions about vaccine allocation
for your district. And we have also provided them with
information from our public health law program, which gives
them the legal guidance from the statutes that are applicable
to them.
Ms. Norton. Well, that is certainly at variance with what I
was told. Therefore, I am asking, by the end of the day, would
you provide me with a copy of that? We were told that you all
did not consider it appropriate to do so. And I am very pleased
if you have reconsidered.
Dr. Gerberding. We consider it appropriate for them to use
their authorities as they see fit.
Ms. Norton. Well, obviously as they see fit. I am not
asking you to demand what you can't demand. I would like to
have a copy before the end of the day so I can make sure my own
public health authority knows that has been your
recommendation.
Mr. Shays. Time has expired and we need to move.
Between Mrs. Maloney and Mr. Sanders, have you worked out
who goes next?
Mr. Sanders. She won.
Mr. Shays. OK.
Mrs. Maloney, you are next.
Mrs. Maloney. Thank you.
First of all, I would like to thank the witnesses for your
testimony.
Just to underscore how critical this challenge is, two flu
outbreaks in New York City alone have led to the death of four
people and 13 hospitalizations in the past few weeks. Our
mayor--and I congratulate him for this action--has reached out
to purchase, along with New Mexico and Illinois, 200,000 doses
of flu vaccine from European suppliers. And while this is not
enough to cover everyone in New York City, it would cover our
high-risk residents and it would supply roughly 570,000 doses
of vaccine.
I wrote a letter, along with other members of the New York
delegation, in a bipartisan way, to Commissioner Crawford,
asking FDA to expedite the process for the review for these
doses, and I really want to know where that is. We need to get
this vaccine. We have wholesalers that are available in Europe
that will sell to us. How soon can we get it approved?
Mr. Crawford. We are going through a process which
involves, first of all, getting the lot numbers of the vaccine,
which the Governors and the mayor have kindly provided. The
company that manufactures the vaccine has authenticated those
lot numbers, they are in fact legitimate production from their
facilities. And what we are now doing is getting what is called
the pedigree, and that is where the vaccine has been, where it
has been shipped to and whether or not it has been kept
refrigerated. We should have all that information in the next
few days and we should be able to make a determination of
whether or not it is suitable very shortly after that. I can't
give you a specific date, but we have up to 750,000 doses
nationwide that we are dealing with, including the 200,000 for
New York City, and we should be able to do all of them at the
same time.
Mrs. Maloney. I would like to ask CDC what the
justification is that you have for not buying the many doses of
vaccine that is available from wholesalers in Europe right now?
That vaccine is available, unlike the vaccine from
manufacturers which may not be available until January, which
may be too late for many high-risk patients.
Dr. Gerberding. I think the answer is the same as the
answer that Dr. Crawford provided. We can't purchase vaccine
until it has been verified that it meets the importation
criteria and has been handled in a way. The vaccine in question
has already left the manufacturer, so it is out in the
wholesale arena, and we are not allowed to purchase that until
we know that it has been properly stored and maintained, and
that its safety can be guaranteed.
Mrs. Maloney. So you are reviewing wholesale production and
sale at this point, CDC?
Dr. Gerberding. We are working with FDA to do everything we
can to get international vaccine sources into this country
safely and quickly.
Mrs. Maloney. I would like to go back to the timing of the
review. The Wall Street Journal this week quoted John Taylor,
FDA's Associate Commissioner for Regulatory Affairs, and he
said that in 2003 FDA's Liverpool inspection showed systemic
quality control issues at the Chiron facility. And yet, even
though FDA knew that they had these problems, you never
returned to the plant to verify that things had been rectified
and that the vaccine would meet minimum safety standards, and
you relied on Chiron's assurances that they had corrected it.
And even after Chiron announced on August 27th that it had
identified contamination in some of the flu vaccine, you still
did not schedule an inspection.
So my question is if FDA had responded quickly to the
August 27th announcement, could we have avoided the severity of
the problem, if you had gone in there early and worked with
them and corrected it, instead of waiting? And then, second, if
you had alerted Aventis, the second company that is verified to
produce the vaccine, of the problem, could FDA have redirected
their vaccine to the high-risk individuals? By the time the
announcement came to Aventis that we had a challenge and that
there was a shortage, they had already shipped almost 60
percent of the vaccine; but it had not been shipped before
August 27th.
So, in short, I think that the American people deserve more
from FDA in their management in a proactive way of making sure
that the vaccine was there and checking on it in advance. But
from this timetable that we have, you didn't even go for an
inspection, you didn't followup, you didn't alert Aventis. And
then there comes another question: Why do we only have two
companies with this vaccine? I shudder to think if it had been
small pox vaccine and we had a breakout of some terrible
disease.
Chairman Tom Davis [presiding]. The gentlelady's time has
expired.
Dr. Crawford.
Mr. Crawford. Actually, we don't control how many companies
want to enter the U.S. market. There is not much we can do
about that. We wish we had the 20 manufacturers we formerly
did.
We did followup on what we found in 2003, and, actually,
the vaccine for that year, which was the subject of that
inspection, turned out to be OK, and it was used. Then a new
batch of vaccine was prepared for this year, during this year.
It was too late in August for them to start over again, because
it takes from roughly January or February until it finally
comes offline for it to be produced. But we have, once we got
the information, gone to other manufacturers, and we have been
able to find millions of more doses, and we are still looking
with the cooperation of Governors in States and elsewhere to
complete as large a quantity of vaccine as we possibly can.
Chairman Tom Davis. OK, Mr. Sanders, you are recognized for
5 minutes.
Mr. Sanders. Thank you very much. Mr. Chairman, the issue
that I want to pursue is a very simple one, and that is the
Federal Government and numerous States, including the State of
Vermont--Dr. Crawford, you and I chatted about this very
briefly, and I discussed it with Secretary Thompson as well
very briefly.
Mr. Crawford. Yes.
Mr. Sanders. The Feds and the States have identified over 5
million flu vaccine doses that are available in Canada and in
Europe. And we are not talking about obviously fly by-night
companies, we are talking about Aventis, we are talking about
Glaxo, we are talking about ID Biomedical in Canada. And to the
best of my knowledge, these flu vaccines have already been used
and distributed in Europe and in Canada, like a new product.
My question is, given the crisis that we face--Mrs. Maloney
mentioned that people in New York are already dying; the fear
is that there could be a serious outbreak of flu--why does it
take so long? I mean, you have reputable companies in countries
which are well regulated, Europe and Canada. You have a product
which has already been distributed to the people in those
countries. Why, last month, did you not send a host of
inspectors there to make the check of the plan, of the dosages,
and get them out to the people? Dr. Crawford.
Mr. Crawford. It won't take very much longer. The process
is basically threefold. These vaccines, although used in other
countries, are not approved for use in the United States, so we
have to speed up that process. The way we do it is we contacted
these three manufacturers, got their production records, and
also what is called their master file of how they produce the
vaccine.
Mr. Sanders. That is the first day. What did you do on the
second day?
Mr. Crawford. The second thing is we sent inspectors, and
they have now all completed their inspection of these
facilities. They will file their reports with me. The first
one----
Mr. Sanders. I don't mean to be rude. We don't have a lot
of time. I understand all that. That is legitimate. That is 2
days' worth of work. Why has it taken it a month?
Mr. Crawford. No, it is about a month worth of work.
Mr. Sanders. Why?
Mr. Crawford. Because you have to get these master files.
First you have to get the cooperation.
Mr. Sanders. Yeah, we have things like email; you have
planes to get you over there.
Mr. Crawford. No, no, no. Let me explain. You have to get
the cooperation of the company; they have first got to decide
that they want to give it to us. That took a lot of stuff.
Mr. Sanders. We have talked in Vermont to some of these
companies; they want to sell their product. You are not giving
me a good--briefly, why does it take----
Mr. Crawford. And then, finally, we have to give them
approval to bring it in under what is called an investigational
new drug application.
Mr. Sanders. All right, I will give you 3 days. This does
not take a month. You have people in my State who are very
concerned. All over this country they are concerned.
Mr. Crawford. I can assure you we will get it as quickly as
we possibly can.
Mr. Sanders. But you see, I want to raise a question, and
tell me that maybe I am being overly concerned here. Some of
us, including the majority in the House, believe in
prescription drug re-importation. We think that it is insane
that Americans have to pay two, three, five times more for the
same product that our friends in Canada and Europe do. If we
had prescription drug re-importation, those products would be
in this country a month ago. I hope very much that, given the
administration's opposition to re-importation, you are not
making this more difficult than it should be. Could you comment
on that?
Mr. Crawford. If the question is are we making it more
difficult than it should be, the answer is no.
Mr. Sanders. But you still haven't given me a reason why,
with all of the resources at the FDA's command, why we have not
approved those medicines and why we have not distributed them.
Mr. Crawford. Well, I told you we are doing it as quickly
as we can, and that it is a matter of days away before we make
a determination about these particular products.
Mr. Sanders. Then how long does it take you to make a
determination?
Mr. Crawford. Well, it depends on what the data is we get,
how we evaluate it, whether or not we can----
Mr. Sanders. All right, explain to the people who are
watching this. You have a product that has been widely
distributed in Europe and Canada; you are inspecting these
facilities of major drug companies, above-board, reputable. How
long is the determination going to take and why is there so
much question?
Mr. Crawford. It is variable. It is normally about a
month's time before we reach an evaluation, because we have to
get all the records, we have to visit the plant, we have to
make a determination. We have to be sure that the vaccine
brought in won't injure the American people.
Mr. Sanders. Well, of course.
Mr. Crawford. By law, it has to be done on an
investigational new drug application, and that is the way it
is.
Mr. Sanders. How long is this determination process going
to take?
Mr. Crawford. It is just about over.
Mr. Sanders. So you think you can make a decision within a
week?
Mr. Crawford. I wouldn't be held to a week, but I think it
could be quicker than that in one case.
Mr. Sanders. All right, now, my question is--and I know you
and I chatted about this----
Chairman Tom Davis. The gentleman's time has expired.
Mr. Sanders. Thirty seconds.
Chairman Tom Davis. If he can state his question quickly.
Mr. Sanders. Thirty seconds.
Chairman Tom Davis. State the question.
Mr. Sanders. All right.
Are you going to allow States and cities to go forward or
are these European and Canadian drugs going to come into the
United States and you guys will distribute it?
Mr. Crawford. We have been working with the States. Some of
them want to bring them in directly, and they already have made
contacts and so forth, so we will work with them on an
individual case-by-case basis.
Mr. Sanders. Thank you very much.
Chairman Tom Davis. If I could just followup. I think you
testified earlier you believe that some of these drugs from
foreign manufacturers are going to be certified and be able to
come in the country.
Mr. Crawford. Some of these vaccines, yes.
Chairman Tom Davis. Vaccines, right. Thank you very much.
Who is next over here? Mr. Tierney, have you asked
questions yet? I think you were here. Would you like 5 minutes?
We still have a couple questioners here.
Mr. Tierney. Thank you, Mr. Chairman.
Dr. Crawford, let me ask you a set of questions here about
Chiron's plant in Liverpool, England. It was subject to an
inspection both by the FDA and by the British counterpart, the
MHRA. Now, you have repeatedly stated that both agencies
responded to the August 2004 reports of contamination in a
similar fashion. I think at the committee's October 8th hearing
you said that both FDA and the MHRA performed inspections that
were about the same thing. In a later press conference with
Secretary Thompson, you stated, ``We would have, 5 hours later,
made the same conclusions as the British; we were in synchrony
with them.''
So I want to just ask about some of the differences between
the British and the U.S. approach to that August Chiron
announcement of contamination. When the initial contamination
was reported, it was the United States, and not the U.K., that
immediately lost several million doses. It was the United
States, and not the U.K., that was depending on Chiron for
about half of its vaccine supply. Yet, it was the British, who
had, I think, much less at stake with this vaccine facility
than the United States, that sent an inspection team to the
facility within a few weeks of the August 25 announcement, and
the British who also sent a second inspection team to the plant
at the end of September. Why didn't our FDA respond forcefully
to the August contamination by sending inspectors to the plant,
as did the British?
Mr. Crawford. We had inspectors in the plant on August 25,
and----
Mr. Tierney. But if I could just interrupt for a minute.
You had somebody there by coincidence, who was inspecting an
entirely separate and discreet issue?
Mr. Crawford. Yes. They were getting up a different line.
But they were there and they were alerted by Chiron. They went
over some records and made some recommendations. Subsequent to
that, we, along with the CDC arranged for a series of calls, at
least once a week, to find out how they were doing with their
bio burden in that plant. Things appeared to be going well up
until the final reports, which came to the British and also
came to us in virtually the same amount of time. They scheduled
an inspection, as did we.
Mr. Tierney. But your inspectors over there did not do the
same kind of thorough inspection that the British team did when
it went in.
Mr. Crawford. I can't speak for the British.
Mr. Tierney. Well, you can speak for yours, and you know
that they did a more thorough examination. Your person did a
somewhat cursory look at some records, but didn't actually have
a full-blown inspection that you ordinarily would have had in
response to this type of an emergency.
Mr. Crawford. Well, we would have come to the same
conclusion based on our lot release program; we would not have
allowed the product into circulation. And I made that decision
following an inspection that took place onsite.
Mr. Tierney. Let me look at another point of difference on
this. The British received a draft of the Chiron inspection
sometime in mid-September, before even their second inspection.
Yet, on the other hand, we never received the report until the
British actually shut down the facility, sometime in October.
How do you explain that the British got that inspection report
so much more quickly than the FDA did?
Mr. Crawford. We were getting a weekly update from the
company, and we were scheduled for the final report on October
5. The Chiron facility was under instruction from the U.S.
Government to quarantine the product, which they did, so none
of it could be released, starting on August 25. So I believe we
had control. In fact, we did have control, because none of it
got out.
Mr. Tierney. But there was a serious gap, and the British
seemed to be on top of this thing. They are getting a report
before their second inspection; we get it weeks later. I mean,
it would seem to me like they were a lot more aggressive, even
though they had less at stake than we did, and I am wondering
why it was.
Mr. Crawford. Well, we got a report every week, but the
final report was scheduled for October 5 for both governments,
because that was the end of the run. You can't get a final
report until they finish.
Mr. Tierney. Well, is it fair to say, though, that the FDA
was caught a little flat-footed about the British closing of
that plant, that the FDA didn't even know it was going to
happen until after the fact?
Mr. Crawford. Well, by law, they could not communicate with
us, and we did not know that they were going to do that on
October 5, no, that is correct.
Mr. Tierney. The law that you are mentioning is a British
law, right?
Mr. Crawford. It is.
Mr. Tierney. But that can be waived. We know that because
it was waived after the fact.
Mr. Crawford. Well, the British issued a press statement
about 3 days after the October 5 determination, in which they
said they were constrained by their law from communicating to
us or the other 98 countries.
Mr. Tierney. But it could be waived, and it was waived
after the fact.
Mr. Crawford. Well, now we are able to work together
because of the company's willingness to share it.
Mr. Tierney. So my question, I guess, is this. It is a very
important source of supply for us.
Mr. Crawford. Yes.
Mr. Tierney. We had a lot at stake. Why would we rely
simply on the company's analysis or report of facts, or
whatever? Why hadn't we asked for a waiver from the company,
which tells us now that they would have certainly cooperated?
Why didn't we ask for information from more than one source as
this thing was developing? Why not say to the company ahead of
time we need a waiver; we want to not only find out from you
what is going on, we want to talk to our British counterparts
and we want to have our own inspections, we want to stay on top
of this thing because we have so much at stake?
Mr. Crawford. We were getting all the information we were
asking for; there was no need to do that.
Chairman Tom Davis. I thank the gentleman.
At this time, Mr. Cummings, you have 5 minutes.
Mr. Cummings. Thank you very much, Mr. Chairman. I really
appreciate it.
Let me just ask you this. I just want to make sure we are
clear. Did FDA make any mistakes?
Mr. Crawford. FDA is not perfect. We followed our situation
here as we traditionally do, and at the end of the time we got
the final report on schedule, October 5. We sent an inspection
team over, and then we had to make the determination that this
vaccine was not usable; therefore, it never got the U.S.
population.
Mr. Cummings. So you are saying that made----
Mr. Crawford. So, therefore, it was a success.
Mr. Cummings. Whoa, whoa, whoa. Excuse me. Are you telling
us that FDA made no mistakes?
Mr. Crawford. In this vaccine thing?
Mr. Cummings. Yes.
Mr. Crawford. No. It never got on the market.
Mr. Cummings. I can't hear you.
Mr. Crawford. It never got on the market.
Mr. Cummings. FDA rejected the recommendations of the
inspectors and decided not to pursue official enforcement
action against Chiron in June 2003. As a result, the problems
at the facility were not public, and told investors that the
inspection showed the plant was really ``in very good shape.''
Was that a mistake?
Mr. Crawford. On the 2003 vaccine production, we asked them
to make some corrections; they did. That vaccine was fine.
Mr. Cummings. So you are saying you didn't make a mistake
there.
Mr. Crawford. No, because the vaccine was fine.
Mr. Cummings. FDA failed to reinspect the facility to find
out if any of the problems were corrected or the company's plan
was being implemented as proposed. Yes or no, was that a
mistake?
Mr. Crawford. We reinspected by taking information from
them all along, so, no, we did not violate our procedures.
Mr. Cummings. So again you didn't make a mistake.
FDA declined to meet with Chiron after it requested a
meeting ``as soon as possible'' to discuss plans to respond to
the June 2003 inspection. This meeting could have helped the
company understand the severity of the problems. Was that a
mistake?
Mr. Crawford. We met with Chiron.
Mr. Cummings. FDA delayed sending a copy of the full
inspection report to Chiron by 9 months, from September 2003 to
June 2004. By the time the report arrived, the time to
implement some of the recommendations mentioned had already
passed. You didn't make a mistake again?
Mr. Crawford. That was a mistake.
Mr. Cummings. Upon hearing of the actual contamination of
vaccine this summer, FDA neither conducted a prompt inspection
nor reviewed the company's records. As a result, FDA was caught
completely by surprise by the British enforcement action. Was
that a mistake?
Mr. Crawford. We did review the company's records.
Mr. Cummings. So no mistake there?
Mr. Crawford. No.
Mr. Cummings. You know, we have a major problem here. We
have people in my district who cannot get these flu vaccines
that are begging for them; seniors, many of them standing in
long lines. But FDA made no mistake. The reason why I asked you
these questions is that we cannot deal with a problem unless we
accept the fact that we have one, that we made mistakes.
Mr. Crawford. We are working to get more vaccine.
Mr. Cummings. So FDA made no mistakes.
Mr. Crawford. Look----
Mr. Cummings. Yes or no?
Mr. Crawford. The vaccine was contaminated in the final
fill. There was no way to know that until October 5, when the
final report came through. You can't do that until it gets
finished. We didn't make a mistake because we condemned the
vaccine; it did not go into U.S. circulation. That was not a
mistake. I would do it again.
Mr. Cummings. So you are saying to the people of the United
States, as they watch you on C-SPAN, that you all made no
mistakes.
Mr. Crawford. As I said, we condemned the vaccine----
Mr. Cummings. Yes or no?
Mr. Crawford [continuing]. And it did not get here. We make
mistakes, but we followed the procedures----
Mr. Cummings. No, I am talking about with regard to this.
Mr. Crawford [continuing]. And we took the right action.
Mr. Cummings. No mistakes.
Mr. Crawford. The vaccine didn't get into circulation.
Mr. Cummings. Fine. Apparently, you don't want to answer my
question. I asked you a question. I said did you make any
mistakes. Did FDA make any mistakes with regard to this?
Mr. Crawford. I already----
Mr. Cummings. Sir, let me tell you something. I have to go
back to my district and I have to explain to them why we have a
Federal agency that, to me, made some mistakes, but refuses to
admit it. At least just say no.
Mr. Crawford. I already told you we made a mistake.
Mr. Cummings. No.
Mr. Crawford. We made a mistake. I can tell you no.
Mr. Cummings. You did? What were the mistakes that you
made, so that we can correct them?
Mr. Crawford. We didn't get the report back to them on time
in 2003; we were late by a few months, and our procedures call
for it to get there in time. We have corrected that procedure,
but that was a mistake.
Mr. Cummings. Let me ask you one last question. During the
campaign season I noticed one interesting thing that happened.
Every time this flu vaccine came up in my district, my opponent
jumped up and said that there are not more companies producing
it because they are afraid of liability. I heard that over and
over again. And then I read in the Washington Post that one of
the main reasons why they didn't produce it is because it has a
short life span, and they were afraid of spoilage and losing
money.
Is that true? Which one is true?
Mr. Crawford. I don't know why they don't enter the U.S.
market. I don't know about liability; I think that could be a
factor. But they have to remake the vaccine every year, and I
am sure that is a factor.
Mr. Cummings. But you are saying you don't know why they
don't enter the U.S. market?
Chairman Tom Davis. The gentleman's time has expired. Thank
you.
Mr. Cummings. He said no. I just want to make sure that is
on the record. He doesn't know why they don't enter the U.S.
market.
Chairman Tom Davis. The gentleman's time has expired. And I
don't think it is productive for Members to be screaming at
witnesses that are here on their own volition. We all have
questions of this.
Mr. Cummings. Mr. Chairman.
Chairman Tom Davis. Now I am going to take my 5 minutes.
The FDA basically followed your standard practices in
waiting for the failure investigation report, right?
Mr. Crawford. Yes.
Chairman Tom Davis. Before proceeding to inspect the
Chiron. And Chiron never did produce the report to you until
after its license was suspended by the MHRA on October 4th.
Mr. Crawford. That is correct.
Chairman Tom Davis. The FDA and MHRA have both told the
committee that Chiron had no reason to expect its license would
be suspended until it completed its failure investigation
report that was provided in draft to MHRA on September 24th.
Mr. Crawford. That is correct.
Chairman Tom Davis. Once Chiron's license was suspended, on
October 4th, U.S. access to the report and investigation by
U.S. authorities was a moot point, although further inspection
confirmed the judgment of MHRA, is that correct?
Mr. Crawford. Yes.
Chairman Tom Davis. The problems at Chiron are not
longstanding ones that FDA should have recognized long ago;
Chiron's license was suspended for systematic problems in the
facility, such as lack of oversight and execution, but not the
specific contamination or other issues addressed in 2003, as
you have stated, and as we have gone through and I think the
reports are clear, is that correct?
Mr. Crawford. Yes, that is correct.
Chairman Tom Davis. The FDA didn't reject the initial
recommendation of the team biologics to refer official action
on the June 2003 issues?
Mr Crawford. No, we did not.
Chairman Tom Davis. And further discussions resulted in
full agreement by all of those involved that voluntary action
was appropriate, isn't that correct?
Mr. Crawford. That is correct.
Chairman Tom Davis. Was there any dissension in that?
Mr. Crawford. No. The team biologics has a very good peer
review of the process, and then they reach a consensus.
Chairman Tom Davis. And there is no evidence that anyone
involved in the process disagreed with the final decision, is
there?
Mr. Crawford. No, there is not.
Chairman Tom Davis. OK. I appreciate it.
Mr. Mica, did you want to ask.
Mr. Mica. Thank you.
Chairman Tom Davis. Well, I am in my 5 minutes. Mr. Shays
will get 5 minutes.
Mr. Mica. You know, you have been hammered. You still
haven't understood this, because you are the bad guy, and we
have to prove you bad.
Mr. Crawford. I am beginning to get the picture, though.
Mr. Mica. OK. But this 2003 mistake that you admitted to,
in not responding in time, now the batch of vaccine, when was
that produced that proved to be bad, was that in 2003?
Mr. Crawford. That was with reference to the 2003 vaccine,
which proved to be good, actually.
Mr. Mica. OK. So the 2003 mistake that you admitted to had
nothing to do with the batch in 2004.
Mr. Crawford. Nothing, absolutely nothing.
Mr. Mica. OK. Well, but see, you are bad, and you have to
pay, because we don't have the drug companies around; we have
less people. Pretty soon you are not going to have anybody to
send warnings to. What the hell are you guys going to do over
there?
Mr. Crawford. It will be a lonely time for us.
Mr. Mica. But it is kind of sad that it has evolved to
this.
I think Mr. Van Hollen had a very good point, though. He is
gone now, but we do have lots of seniors that want that. We
should be manufacturing this in the United States. And Mr.
Waxman is right. Even though he attacked me personally, I have
to say he is right. We don't have a liability problem now
because we have just about run out of people to sue. So he is
right on one account. But you have to adjust liability.
Dr. Gerberding, she went down all of the problems: you have
a short shelf life; you don't have a guaranteed market, so
people don't produce it; you have regulations that impede the
production in the United States; you have a guaranteed purchase
program of childhood vaccines that actually pays less than I
think the cost, and that has also inhibited the manufacturing
in the United States. So it is a host of these issues. And
until Congress addresses these issues and changes some of the
law regulations that we have in place, in fact, we won't be
producing these vaccines in the United States.
Just a quick question, doctor. Wouldn't it be a lot easier
for you to keep tabs on these manufacturers if they were in the
United States, rather than far-flung around the globe?
Mr. Crawford. It certainly would be easier to get to them.
We don't have any overseas locations at FDA, we have to
dispatch our teams of inspectors from here.
Mr. Mica. OK.
And guaranteed purchases, Dr. Gerberding, that is also
something that needs to be addressed?
Dr. Gerberding. I don't have the right formula for a
solution, but everything is on the table right now, and in
order to guarantee a market, that would be one strategy that we
could look at to ensure the manufacturers that their vaccine
would be purchased.
Mr. Mica. And the government now buys 60 percent of the
pediatric vaccines. Is that still the case? That is the
information that I have.
Dr. Gerberding. I believe that is correct, but I can get
you the exact percentage.
Mr. Mica. Thank you.
Chairman Tom Davis. OK, we are just about up. Thank you.
Let me just add. We had an old saying when I used to
practice law, that if you have the facts, you pound the facts;
if you have the law, you pound the law; and if you have
neither, you pound the table. I think in this it is pretty
clear from the record that you have set out earlier today that
you followed the appropriate procedures, you followed the
appropriate protocols. We may need to tweak those protocols a
little bit. I mean, we need to make sure what happened this
year should never happen again.
Mr. Crawford. Absolutely.
Chairman Tom Davis. And I think we need to have that dialog
of how best to prevent it. It seems to me that the most basic
thing we can do is make sure there are more suppliers. As Mr.
Sanders and others have pointed out, there are foreign
suppliers who haven't asked for U.S. recognition, but we need
to get them into our markets and have you out there inspecting
them. And if we do that, at least we have some guarantee of
alternate sources of supply. There are other issues we need to
look at, but we will talk about that.
Mr. Shays has 5 minutes a little later, and we will talk
about that.
Ms. Watson has not had her 5 minutes yet. Diane has been
patiently waiting over there.
Ms. Watson, you are recognized for 5 minutes.
Ms. Watson. Thank you, Mr. Chairman, very much.
And thank you, doctor, for being willing to sit on the hot
seat. We are not going to talk about that or good guys. I just
would hope that you would clarify some things for us. So I am
going to raise two issues, and then you can just address them
together.
The first thing, I understand that Chiron is based in my
own State of California, yet we manufacture in the United
Kingdom for the U.S. market, and I am wondering why we could
not start building a plant in California, why Chiron could not.
That ought to be something that we ought to be talking to them
about. And Aventis, I understand, is a French firm, but they
manufacture in Pennsylvania.
So is it possible to produce the supplies that we are going
to need? And I will imagine our need will be greater in 2005 in
California and Pennsylvania. You can answer that after I finish
with my next comment.
The next comment is that I understand in June 2003, after
the inspection, the company asked to meet with the FDA. Is it
true or not that the FDA refused to meet with Chiron to discuss
its problems? So can you clarify what is going on? It is
essential, if they are one of two producers for the U.S.
market, that we be communicating with each other.
So can you clarify those issues for me, please?
Mr. Crawford. Yes. We did meet with them. I have actually
met with them myself, so that is not correct.
Ms. Watson. Can you give me a time?
Mr. Crawford. We can supply that for the record, yes.
Ms. Watson. Has it been after 2003?
Mr. Crawford. Yes. And with respect to the fact that there
are no vaccine production facilities owned by American firms in
the United States, I believe Chiron is going to testify on the
next panel, and you may wish to ask them. I think what guides
them to seek facilities elsewhere is because the facility is
available. In other words, I believe in mid-2003 Chiron
actually acquired this plant from another company, and they
didn't even own it until that point. The facility that is in
Pennsylvania I also believe was previously owned by another
corporation. So I think even though a French company
manufactures there is because the plant was present.
Now, what do we do about getting plants built in the United
States? That is beyond my authority or expertise, but I would
think what we are doing will help some, and that is we are
engaging the CEOs of all the companies in the world that
produce flu vaccine, and we are telling them that FDA has a
commitment to help them get up-line and get moving to either
enter the U.S. market or to build a facility in the United
States. We will help them with whatever we can do. We can't
force them to do that, though, and that is why I responded as I
did to the last questioner.
Ms. Watson. I think that as the Federal Drug
Administration, and with the threat of maybe a biological war,
a threat of biological vaccines coming in that are very toxic,
I would think that the FDA would want to suggest that we have
legislation requiring that we develop our own plants under the
regulations that you already have. I see the need as being
tremendous, with the threat that is facing the United States
and the rest of the world from the terrorists. We need to be
ready. I would think that would be a readiness plan that would
be recommended from the FDA. We should never find ourselves in
this position again.
And as Elijah Cummings said, people are coming into my
office in the center of Los Angeles in tears, and they are
rushing around to see if they can find a place to get their flu
shots. And I am telling them don't get one, it probably will
give you the flu, because they do inject some of the, as I
understand, the microbes.
But please, please, as FDA, don't wait for us as the
legislators to do it; you need to come with a strong
recommendation and we need to get the building of the plants
and the distribution of these needed vaccines right here in the
United States.
Thank you, Dr. Crawford.
Mr. Crawford. Thank you.
Dr. Gerberding. Mr. Chairman, may I just say one thing?
Chairman Tom Davis. Yes, Dr. Gerberding. Sure.
Dr. Gerberding. I would just like to emphasize that the
injectable flu vaccine does not contain live virus that causes
the flu; there is no risk of getting the flu from the vaccine.
The nasal vaccine does contain a weak flu virus, so there is a
theoretical risk of getting flu from that product, but not the
injectable vaccine.
Ms. Watson. Let me just respond by saying regardless, I
think they ought to be manufactured here, the nasal or the
injectable. We ought not to depend on other nations for our
tremendous need.
Dr. Gerberding. I absolutely agree with you on that. Thank
you.
Ms. Watson. Thank you.
Chairman Tom Davis. Mr. Shays, you are recognized for 5
minutes.
Mr. Shays. I thank the gentleman.
It is a wild circumstance. We have an American company
whose product made in England and we have a French company
whose product is made in Pennsylvania. And what I am interested
to know, Dr. Crawford, is if you had realized even 5 months
earlier that we had a problem, there would have been no
solution, or would we have been able to go out and request
vaccines from other places and been able to deal with this
problem?
Mr. Crawford. The eggs, which are chicken eggs, are
actually----
Mr. Shays. I need a short answer.
Mr. Crawford. It started too early, so we couldn't have
done anything about it.
Mr. Shays. So it speaks to a much bigger issue.
Mr. Crawford. Absolutely.
Mr. Shays. I just want to align myself with Mr. Davis and
also Mr. Mica. This is a huge problem, but the fault does not
rest at your doorstep; it rests right here in Congress, working
with the three of you.
I would like to ask Dr. Gerberding, on October 25, 2004,
the CDC introduced a secure electronic system to display
influenza vaccine dosage distribution information called the
Flu Vaccine Finder. This dataset is only available to State
health officials. Has the Flu Vaccine Finder proven to be an
effective tool for States to identify and reallocate available
vaccines?
Dr. Gerberding. The Flu Vaccine Finder is an unprecedented
way for States to see the proprietary information about vaccine
delivery in their jurisdiction. I believe they are finding it
to be extremely helpful. The feedback we have received so far
has been enthusiastic and with great relief. They can finally
get their hands on the information about distribution planning
that they need. We are working to make that same kind of
information available to people at the local health department
level as well; that just takes longer because there are several
thousand of them.
Mr. Shays. Before I ask you the next question, I want to
say that the imminent biological threat facing the United
States I think is pandemic influenza, as a mutated viral form
has caught the world unaware in the past, and it will do so in
the future. SARs was a huge opportunity for us to see how we
would deal with this issue. It was involuntary and it was life-
threatening, and it was extraordinarily serious. I think it
points out persistent weaknesses in public health surveillance
and vaccine production surge capacity to meet emerging threats,
and I would like to know if you agree.
Dr. Gerberding. I agree. But I also think that the
investments we have made and the lessons we learned from SARs
have been very helpful to us in dealing with this current flu
season situation, and we are learning lessons from this
situation that will help us be even more prepared for a
pandemic flu. In fact, that is part of our mission right now,
is to look at the distribution process, to look at our
detection capabilities, look at our surge and make sure that we
are learning from that so that if we see pandemic flu emerge,
we can be better prepared.
Mr. Shays. So what I want to ask the three of you is I am
asking do we need a new mechanism, new incentives to guarantee
to that adequate numbers of safe and effective flu vaccines are
produced and delivered annually? Just in this more particular
case I guess the answer is yes. And then with the very short
period of time remaining, tell me what that is.
Dr. Fauci. One of the things from a research standpoint,
very briefly, is to provide the advanced technologies to allow
the companies to be able to get a head start, since we
obviously have to partner with them to get the vaccine
developed and out in an emergency situation. I mentioned a
couple of them in my presentation. And that is one of the ways
we can do it, by providing the technology through the science.
That is one of several ways.
Mr. Shays. And provide economic incentives that they are
willing to do that.
Dr. Fauci. Oh, absolutely. And that gets to the point that
you were making There are four or five issues that we need to
do. It is a risky business; it is not a high profit business.
We have to not only provide the technologies that I mentioned,
but some of the things that Dr. Gerberding early on mentioned
and Mr. Mica questioned, something like guaranteed purchases,
cutting down some of the red tape which we call regulatory
relief. And liability fits in there. It may not be the biggest
one, but it is one of several things we can do.
Mr. Shays. I agree.
Chairman Tom Davis. Thank you very much.
Well, let me say to this panel thank you. Dr. Crawford,
that is it. We don't have any more questions. I know you are
sorry to hear that. You have accorded yourself well. All of you
have. And we appreciate very much your time and your expertise
on this. You are no strangers to this committee. We look
forward to working with you in the future as we consider these
issues. Thank you very much.
The committee will take about a 3-minute recess as we get
ready for our next panel.
[Recess.]
Chairman Tom Davis. Thank you. We are moving to our next
panel.
I want to thank our witnesses for appearing. Invited to
join us on our second panel are two vaccine manufacturers to
discuss vaccine production capacities to respond to the
shortage crisis in ways to ensure a stable annual flu vaccine
supply. Dr. Howard Pien, who is the president and chief
executive officer and chairman of the board of Chiron, will be
providing testimony. We also have Kathleen Coelingh of
MedImmune, which manufacturers the nasal spray vaccine,
FluMist, which was referred to earlier. And Dr. Robert Stroube,
who is the Virginia State health commissioner, also joins us.
He is here on behalf of the Association for State and
Territorial Health Officials to provide an assessment of State
and local public health departments' ability to respond
adequately to the vaccine shortage. And last but not least, Dr.
Jerome Klein is here from the Boston University School of
Medicine. He will be providing a more academic perspective into
issues surrounding the annual influenza vaccine.
It is our policy that we swear everybody in before you
testify, so if you would rise with me and raise your right
hands.
[Witnesses sworn.]
Chairman Tom Davis. Thank you.
Let the record show everybody is here on their own
volition. We appreciate very much your being with us today. I
think you know the rules; your entire testimony is in the
record. You have 5 minutes to say whatever you want. I think
you know when the lights come up.
Dr. Pien, we will start with you. And I know this has been
an interesting 6 months or so for you, but we appreciate your
working with us, working with our committee staff here and in
London, and we are pleased to have you here. Thank you.
STATEMENTS OF HOWARD PIEN, PRESIDENT, CHIEF EXECUTIVE OFFICER,
AND CHAIRMAN OF THE BOARD, CHIRON CORP.; KATHLEEN COELINGH,
SENIOR DIRECTOR, REGULATORY AND SCIENTIFIC AFFAIRS, MEDIMMUNE,
INC.; DR. ROBERT STROUBE, VIRGINIA STATE HEALTH COMMISSIONER,
ASSOCIATION OF STATE AND TERRITORIAL HEALTH OFFICIALS; AND DR.
JEROME KLEIN, PROFESSOR OF PEDIATRICS, BOSTON UNIVERSITY SCHOOL
OF MEDICINE
Mr. Pien. Thank you, Chairman Davis and members of this
committee. I welcome the opportunity to appear at this hearing.
In light of Chiron's strong tradition of commitment to
global public health, our vaccine division's inability to
provide influenza vaccine to the United States for this season
has been a painful experience from which we are all learning a
great deal. As we have said on numerous occasions in the past,
we profoundly regret that we have been unable to supply
influenza vaccine for this season. And we appreciate the
opportunity to engage in these very important discussions.
I respectfully suggest that the lessons learned from this
year's experience provide an excellent opportunity to reflect
on the critically important policy initiatives that the 109th
Congress should consider to ensure a reliable and stable
influenza vaccine supply for the United States in the future.
I will focus my remarks on three key messages: what we are
doing, what is our prospect, and what are the policy
considerations that have emerged from this experience.
First, Chiron Vaccines is proceeding expeditiously in
implementing internal changes and devoting resources to enable
it to regain its U.K. vaccines manufacturing license and to
address the concerns raised by the FDA. In the past several
weeks, Chiron Vaccines has developed a plan to implement a
series of fundamental personnel changes that will restructure
the management of our Liverpool operations. These personnel
changes will leverage the strength of Chiron's existing global
management team and will be supplemented by new management to
help take us forward in managing the Liverpool facility. These
changes will maximize our ability to enhance our prospect to
meet the challenge of returning to influenza vaccine
manufacturing for the 2005-2006 season.
We have assembled a world-class international team of 70
internal and external individuals with expertise in quality
control, quality assurance, manufacturing, and regulatory
standards to conceptualize and implement a remediation plan. We
have retained external consultants who have substantial
experience with the United States and the U.K. regulatory
standards. Most importantly, upon the approval of the
implementation plan by our board of directors, this team will
be empowered to make changes that will restore the confidence
of our regulators, both here and in the United Kingdom.
Also, effective November 3rd, I reorganized Chiron's senior
management team to allow me to focus more attention on
overseeing the Vaccines Division's remediation activities at
Liverpool. To that end, I have appointed an interim chief
operating officer of Chiron in Jack Goldstein, previously our
president of the Blood Testing Division. Starting November 4th,
Jack began overseeing our operations other than those related
to Fluvirin remediation.
To my second point. By devoting these resources to the
remediation of our Liverpool facility, we expect to meet and
exceed the required responses to the MHRA and the FDA
observations raised in their respective inspections.
Chiron Vaccines acquired the Liverpool facility in July
2003. Although both the regulatory community and ourselves
recognized it was a somewhat older facility, we promptly
committed to replacing the influenza vaccine production plant
with a state-of-the-art adjacent facility estimated to cost
$100 million, which is under construction. We also proceeded to
address a number of the concerns identified by the FDA in its
June 2003 inspection conducted when Liverpool was under
previous ownership. At present, in coordination with both the
MHRA and the FDA, we are close to finalizing a detailed
remediation plan for our Liverpool facility. The plan covers a
range of enhancements to our manufacturing processes, quality
systems, and structure for management oversight. Subject to the
concurrence of both regulatory authorities and approval by our
board of directors, we will implement this plan expeditiously,
with the hope and the aim of supplying influenza vaccine next
season.
Our ability to regain our U.K. influenza vaccine
manufacturing license in time to participate in vaccine
production next year is mission-critical for Chiron Vaccines.
This plan addresses quality systems in a holistic manner and is
proposed with the aim of exceeding the specific regulatory
observations made last month by the MHRA and the FDA. The plan
covers personnel, processes, equipment, systems, and
infrastructure. The organizational changes will enable us to
entrench a culture of quality where employee performance is
correlated clear and quantitated performance metrics.
To successfully achieve its remediation objectives and to
be able to provide influenza vaccine next year, extraordinarily
close coordination between the MHRA and the FDA will be needed.
In the meetings that we have held with these regulatory
authorities since October 5th, we are heartened by the
encouragement we have received. Having said that, it is
important to add two cautionary notes. In light of the broad
and ambitious scope of our remediation plan, there can be no
conclusive assurance that we will be able to meet expectations
of the MHRA and the FDA by March 2005, which will be the start
of full-scale manufacturing season. Moreover, because the
regulators' GNP standards are ever-rising, we cannot say
definitively whether we will be able to meet them in future
years.
To my third and final point. This year's experience
provided lessons that can enable us to strengthen our national
public policies with regard to interpandemic and pandemic
influenza. We know we must address short-term and long-term
policy objectives that assure a stable supply of influenza
vaccine that drive uptake for vaccine and that establish
manufacturing capacity within the United States. In the so-
called normal influenza season, a stable vaccine supply for the
U.S. market is dependent on diversifying the manufacturing
base, which is in turn driven by an environment conducive to
multiple manufacturers. This environment should have the
following characteristics: (1) sufficient demand to enhance
production capacity; (2) pricing and reimbursement that justify
investments in maintaining and expanding existing production
capacity; (3) a regulatory pathway that fosters innovation in
new technologies; and (4) mechanisms to reasonably protect
vaccine manufacturers from liability claims.
Marketing of influenza vaccine is dependent upon an
effective public and private partnership that improves
vaccination rates by raising awareness, dispelling myth, and
extending the immunization season. In the long-term in order to
effectively address our public health needs in the event of a
global influenza pandemic, a strong public-private partnership
is paramount, particularly to prioritize and allocate influenza
vaccine in the event of a supply challenge. The essential
ingredients for meeting this challenge are evident:
information-sharing, partnership, frequent communication, and
hard work. The public health system is coping with the
challenges, and I believe will emerge stronger from this
experience, with a clearer focus on strengthening our influenza
immunization infrastructure and creating a sustainable
influenza market. The men and women of the public health
service have demonstrated incredible leadership in addressing
public distress and in getting vaccine to those who need it
most in the current supply shortage.
With that as a backdrop, to increase manufacturing capacity
in the United States, the government should begin now to invite
additional manufacturers into the U.S. market and to provide
appropriate financial incentives and clear regulatory guidance.
Experience teaches us, as you said, Mr. Chairman, that
establishing this capacity likely will take several years.
However, events occurring with regard to the avian flu in the
pacific realm indicate that the pandemic clock is already
ticking; thus, we cannot afford any delay.
I ask, respectfully, that my written testimony be also
included as part of the record, and I am prepared to answer any
questions.
Chairman Tom Davis. Without objection, the entire testimony
of all of you will be a part of the record.
[The prepared statement of Mr. Pien follows:]
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Chairman Tom Davis. Dr. Coelingh, thank you for being with
us.
Ms. Coelingh. Good afternoon. My name is Dr. Kathleen
Coelingh, and I am the senior director of regulatory and
scientific affairs and MedImmune, a Maryland-based vaccine
company that manufactures the innovative intranasal influenza
vaccine, FluMist. Approved by the FDA last year for healthy
persons 5 to 49 years of age, FluMist is the first advancement
in influenza prevention in 50 years.
We are at a critical juncture in defining what the
influenza vaccine market will look like in the future and how
U.S.-based vaccine manufacturers will meet the needs of this
country going forward. What will be the incentives for
companies to build U.S.-based manufacturing facilities? How
will our government drive vaccine acceptance, utilization, and
demand, since it is demand that ultimately determines the
supply of vaccine manufactured? And what will be the incentive
for continued innovation?
MedImmune recommends that this committee support and
encourage two key longer term solutions in the realm of policy
changes and incentives for innovation. The first recommendation
is to move toward adoption of a universal recommendation for
influenza vaccine for all Americans. The current
recommendations, which are based on age groups and an ever-
expanding list of underlying chronic medical conditions are
both complicated for the health care provider to follow and are
confusing to the public. We believe that a universal
recommendation will stabilize demand for vaccine, thereby
leading to increased vaccine supply and ultimately to
substantially lowering the current morbidity and mortality due
to influenza.
As an interim step, MedImmune recommends required
vaccination of school-aged children, who have a very high
influenza attack rate and spread influenza to younger siblings,
their parents, and their grandparents. Thus, vaccination of
school children would directly benefit not only the children
themselves, but may also have the potential to greatly reduce
the impact of influenza in our communities. This concept of
protecting an entire community by vaccinating the school-aged
children has already been demonstrated in Japan and in studies
in the United States. In conjunction with this interim step,
money must be appropriated to expand the education of the
public and the medical community about the seriousness of
influenza and the value of influenza prevention.
The second solution that MedImmune recommends to ensure
continued influenza vaccine supply is to provide tax incentives
for scientific innovation and for construction of U.S.-based
facilities. MedImmune is a primary innovator in the area of
molecular techniques, termed ``reverse genetics.'' The use of
reverse genetics is vital to producing seeds for an H5N1
pandemic vaccine, as we heard from Dr. Fauci earlier. MedImmune
owns multiple patents in this area and has granted free access
to its reverse genetics intellectual property not only to
governmental organizations, but also to other companies who are
developing pandemic influenza vaccines. MedImmune is currently
collaborating with the National Institutes of Health to produce
intranasal pandemic vaccines and to test them in clinical
trials.
MedImmune also has core expertise in the innovative area of
cell culture manufacturing. The main advantages of
manufacturing using cell culture are elimination of our
dependence upon egg supplies and more consistent and rapid
production, which will be critical in the event that the egg
supply is decimated by the emergence of a pandemic virus. The
transition from egg-based to cell-based manufacturing will
require considerable investment in the construction of new
facilities and potentially additional clinical studies. Tax
incentives to subsidize the cost of such innovations are
necessary to guarantee a more stable vaccine supply on a yearly
basis and when the pandemic comes.
The government also needs to incentivize manufacturers to
build manufacturing facilities within the United States. There
is an increased risk that, with offshore manufacturing,
companies will face political decisions that may prevent
vaccine products from entering the United States, particularly
in the event of a catastrophic pandemic. Tax incentives for
U.S.-based manufacturing facilities would encourage
manufacturers to build more facilities in the United States.
To address what MedImmune has done during the current
vaccine shortage, since October 5th, we have worked diligently
with the appropriate authorities to, first, blend and fill our
excess bulk vaccine to produce an additional 2 million doses of
FluMist, bringing our total production for this year to 3
million doses; second, we have supplied the Department of
Defense with up to 400,000 doses, the CDC with 125,000 doses,
and we have supplied hospitals with over 60,000 free doses of
FluMist this year; third, we have supplied the FDA with new
storage data for FluMist, which they have promptly reviewed and
approved, allowing the additional 2 million doses of FluMist to
be stored in a household freezer without the requirement for
the special freezer box; and, finally, we have worked closely
with the CDC and the Advisory Committee on Immunization
Practices to clarify that FluMist is an option for all healthy
people 5 to 49 years of age who want to consider protecting
themselves from influenza this season.
Shifting gears a bit and looking forward to next season,
you must understand that the influenza vaccine manufacturing
campaign for the 2005-2006 season is starting right now. We are
already preparing the new vaccine seeds that we anticipate will
be in the next year's vaccine, and we are making decisions
about how many doses of vaccine we will manufacture, including
deciding how many chicken eggs to order. Thus, the amount of
FluMist that will be available next season will soon be fixed.
With some additional regulatory cooperation, MedImmune has
the capacity to produce between 8 to 10 million doses for next
season. These regulatory actions include: FDA approval allowing
for the production of larger lot sizes and filtration;
acceptance by the FDA of our application to permanently
eliminate the requirement for the FluMist storage box; and,
finally, FDA acceptance of recently sumitted data that supports
the expansion of the FluMist indication to include the 30
million healthy Americans who are 50 to 64 years old, a group
that is not eligible for the injectable flu shot this season,
and may not be eligible again next season, should we experience
a continuing shortage.
In summary, MedImmune is clearly at a crossroads in
determining not only how much FluMist will be available next
season, but also whether our investments and innovation will be
recouped in this market. Our level of production for next
season depends on the occurrence of several immediate
regulatory actions. But whether MedImmune expands its
production and whether companies continue their efforts to
develop influenza vaccines depends in large part upon the
government's commitment to encouraging innovation and driving
demand. Requiring childhood influenza vaccination as an interim
step toward a universal recommendation and legislating tax
incentives for both scientific innovation and U.S.-based
manufacturing will go a long way to ensuring an adequate supply
of influenza vaccine in the near future.
Thank you.
[The prepared statement of Ms. Coelingh follows:]
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Chairman Tom Davis. Thank you for your testimony.
We will hear now from Dr. Robert Stroube, Virginia State
health commissioner with the Association of State and
Territorial Health Officials.
Welcome, sir, and you are recognized.
Dr. Stroube. Thank you, Mr. Chairman.
Mr. Chairman, distinguished members of the House Government
Reform Committee, my name is Robert Stroube. I am the health
commissioner in Virginia. I am honored to be testifying before
you today, and I would like to thank you for convening this
hearing on this really crucial problem that we are facing.
The ongoing flu vaccine shortage continues to present many
challenges for Virginia, as well as the other States. State and
local health departments have been working nonstop since
October 5th to address this issue.
As of today, Virginia Health Department has received a
total of 159,565 doses of flu vaccine, which we have
distributed to our local health departments and our long-term
care facilities for administration to people at high-risk of
complications from the flu. In addition, the Health Department
has received 84,480 doses of flu vaccine intended for high-risk
children who are eligible for the Vaccines for Children
program. According to recent information from CDC, we are
expecting another shipment of about 150,000 doses, which we
will allocate to long-term care facilities, hospitals, and
other health care facilities with unmet vaccine needs.
The Health Department is now providing the flu vaccine to
many more people and providers than we would during a typical
flu season. You might say that the Health Department is now the
broker in the management of the flu vaccine to help ensure that
the vaccine goes where it is most needed.
We applaud the reallocation efforts of CDC and of Aventis,
and we are grateful for the timely receipt of the vaccine that
we have. We firmly believe that as the public health agency for
Virginia, it is our responsibility to guide allocation
distribution of vaccine to those who are most in need.
However, we do want the committee to be aware of the
immense workload this situation has placed on local and State
Health Department personnel. During the first week of November,
the State Health Department distributed more than 77,000 doses
of vaccine to our 35 local health districts on a population-
based formula. Each health district developed a flu vaccine
distribution plan based on the needs of the high-risk persons
in that community. In developing those plans, all the health
districts had to make difficult decisions on how to distribute
the limited amount of vaccine. In some areas they opened up
phone lines and began taking appointments on first call-first
served basis; some distributed the vaccine to health care
providers in the community; some pre-identified high-risk
individuals who were unable to get the vaccine in the private
sector.
In Chesterfield County, just outside of Richmond, the
health department there held a ``drive through'' flu clinic
this past weekend so that high-risk people wouldn't have to
stand in line out in the cold. That one clinic required 120
staff members to manage all of the logistics. The health
director there estimates this ongoing issue has required more
than 600 hours of work from senior-level managers, supervisors,
and other personnel. The health department's time devoted to
this ongoing flu shortage supply issues means time away from
other important public health practices.
Another example is our ongoing distribution of 82,000 doses
of vaccine to long-term care facilities in Virginia who did not
receive flu vaccine. In order to accurately determine which
facilities still needed vaccine, all of our 35 health districts
surveyed each facility in their community. The health
department usually does not provide flu vaccine directly to
long-term care facilities. Most of these facilities ordered
vaccine this year through a distributor or directly from the
manufacturer, and most ordered through Chiron Vaccines.
In our Immunization Program, we typically only need one
full-time person working on the flu vaccine program. This year
we have four staff persons working continuously managing the
issue at the State level. In addition, the issue has required
the involvement of all our senior-level management, our public
information personnel, and some of our emergency preparedness
personnel, which manage State level planning, logistics
communication and coordination. We owe a tremendous amount of
gratitude to our hardworking and dedicated public health
employees who are spending hours planning and executing flu
vaccine clinics or answering phone calls from our worried
elderly and our other high-risk citizens. I would like to take
this opportunity to personally thank each and every person for
their service to our citizens.
At the beginning of the shortage, one of our biggest
difficulties was determining how much flu vaccine was available
in the private sector. We would like to thank CDC and Aventis
for their efforts to make this information about vaccine
distribution in the private sector available to us through our
secure Web-based data base. This information has helped us to
identify geographic gaps in vaccine supply and focus our
distribution efforts to providers in those areas. This system
is constantly being upgraded, and just this morning, before I
left to come here, we found out that they have now upgraded it,
so we will be ordering our vaccine directly and sending it
through reallocation out over this data base.
Even with all the flu vaccine now coming to Virginia, we do
not expect that we will have enough vaccine for every high-risk
individual in Virginia this year. To help alleviate the
situation, we continue to provide the public with useful tips
for preventing the spread of flu in the absence of vaccine,
such as frequent hand washing and staying home from work when
sick. In addition, we have been encouraging the use of
pneumococcal vaccine among the elderly and individuals with
chronic medical conditions. This widely available vaccine can
help prevent pneumonia, which in many cases is a secondary
complication of flu.
We would like to thank CDC and the Department of Health and
Human Services for all the work they have done to help manage
the situation and secure flu vaccine for the State health
departments. We believe that everyone involved at the Federal,
State, and local level has done an outstanding job addressing
the problem.
But I cannot stress enough how important it is for Congress
to take steps now to prevent this flu vaccine shortage from
occurring again. This situation has required an enormous amount
of time and effort to manage, and has had a major fiscal and
human resource impact on other important public health
activities.
Efforts must commence now at the national level to ensure a
stable flu vaccine supply. As many of us have stated in
previous testimony, the present system of vaccine production
distribution is incapable of effectively and efficiently
responding to the current demand for the flu vaccine. It is
imperative that Congress take steps now to support the
development of a more reliable and flexible vaccine production
and distribution process. In addition, efforts need to be made
now to guarantee an ample supply of flu vaccine from multiple
manufacturers.
Given the estimated 36,000 people that die each year in the
United States from the complications of flu and the threat of a
flu pandemic, I believe addressing the flu vaccine production
and distribution problem has to be of the highest priority for
Congress.
Thank you.
[The prepared statement of Dr. Stroube follows:]
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Chairman Tom Davis. Dr. Klein, thanks for being with us.
Dr. Klein. Thank you very much, Mr. Chairman. I am Jerome
Klein, a pediatrician, a professor for pediatrics at Boston
University, and a member of the National Vaccine Advisory
Committee.
A robust domestic vaccine capability is a necessity not
only for old threats such as influenza, but for new and
virulent microorganisms spread by natural means or by
bioterrorist activity. The current shortage of influenza
vaccine underlines the vulnerability of the supply of all
recommended vaccines in the United States, and I would like to
touch on four areas that have already been discussed in part in
the prior discussions: first, the loss of vaccine manufacturing
capability in the United States; second, the issue of
stockpiling; three, Food and Drug Administration regulatory
practices; and, fourth, the liability concern.
First, the loss of manufacturing capability. Vaccine
manufacturing is complex, involves uncertainties that do not
exist in pharmaceutical drug manufacturing. There is no
question that additional influenza vaccine manufacturers this
year, if available, would have diminished the effect of loss of
the Chiron product. Companies leave the marketplace when a
product no longer provides a reasonable return on investment.
Appropriate incentives must exist that encourage companies to
enter and remain in the vaccine business. What is needed now is
a sustained effort to provide concrete proposals that will have
a durable effect. A multi-disciplinary group to include all
stakeholders should be convened to evaluate and propose
appropriate incentives for manufacturers to ensure supply of
existing vaccines and stimulate development of new vaccines,
and that is the encouragement of domestic vaccine producers,
not seeking vaccine overseas.
Second, the issue of strengthening vaccine stockpiles. A
program to stockpile vaccines has been available since the
1980's. The principle is simple: government purchase of vaccine
provides a repository that can be called on if there is an
emergent need. Subsequent to the 2002 workshop held by National
Vaccine Advisory Committee, there was additional funding that
was provided to expand the stockpile program. However, no new
vaccine has been added because of a Securities and Exchange
Commission accounting regulation that bars vaccine
manufacturers from claiming sales to the stockpile program as
revenue until they come out of the stockpile. This impediment
to a universally approved response to enhance vaccine supply
should be remedied as soon as possible, because a new influenza
vaccine is prepared each year and the stockpile concept is not
applicable. A redundancy of supply has been suggested. The
government purchase program would be expanded so that
additional vaccine beyond that required for patients at risk
would be instituted. Since influenza immunization would be a
value for healthy children and adults, the additional vaccine
would not be wasted.
Three, streamlining the regulatory activity of the Food and
Drug Administration. The current good manufacturing practices
need to be dynamic, with changes to maintain or improve
facilities to current standards, but allow sufficient
flexibility to ensure continued vaccine production. In
addition, a review of current GMP and regulation should be
instituted to consider whether the complexity of manufacturer
of vaccines and biologics warrants a separate and different
mode of regulation than that used for drugs, which is the
practice currently.
Finally, the liability issue, which, as I understand it has
little role in the current concern about the contamination
issue at the Chiron facility. But there is renewed concern
about litigation associated with the manufacture and
administration of vaccines. The National Childhood Vaccine
Injury Compensation Program was established in 1986 to
compensate quickly and appropriately individuals who suffered
serious injuries associated with the administration of an FDA-
approved vaccine. The program removed the threat of liability
from the manufacturer, as well as those who administer
vaccines, and successfully stabilize the market. The VICP
should be maintained and strengthened to include additional
vaccines. When those additional vaccines are added, additional
staff will be needed. So the VICP program needs to be
supported. Strengthening the VICP would benefit manufacturers,
providers, consumers, and further safeguard the Nation's
vaccine supply.
The development of safe and effective vaccines during the
past 50 years, since the introduction of the polio vaccine, has
been one of the great success stories of American medicine.
However, there is concern, as has been discussed today, that
future contributions of the vaccine industry may be jeopardized
by lack of attention to basic issues. Solutions are not easy to
come by in a sustained effort. The collaboration of all
stakeholders and political will will be required.
Thank you very much.
[The prepared statement of Dr. Klein follows:]
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Chairman Tom Davis. Well, thank you, and thank all of you
for your testimony.
Let me just, if I could, recognize we have with us today in
the back of the room Cub Scouts Pack 1134, Den 7, from the
Chain Bridge District. And we are happy to welcome you here
today to today's hearing. This is on the flu vaccines in the
United States and the shortage we are having.
Let me just start with one question before I recognize Mr.
Mica; and this goes really to Mr. Pien. Could you tell us what
happened at Chiron's Liverpool facility that ultimately led to
the October 5, 2004 license suspension?
Mr. Pien. Yes, Mr. Chairman. Chiron, as I testified,
acquired this facility in July 2003, and the acquisition
actually was conditioned upon a successful satisfactory
inspection that took place in June 2003. And after we made the
acquisition, of course, we continued the investment program, so
about another $50 million got into this current facility. Since
then, in addition, we recognized that, as the standards of
quality will be rising, that we need to build a new facility;
and, therefore, we made the commitment of spending $100
million, as I testified, to build an adjacent facility, of
which roughly $30 million have now been spent.
We had a terrific 2003 season, as Commissioner Crawford had
indicated; we had a 40 percent increase into the U.S. market
from that facility over 2002. We had a 30 percent total output
increase, some of which of course, went to parts outside of the
United States. We found that the facility was viable. We had
tremendous confidence in the ability for that facility to
continue to produce products. And, of course, you will recall
last year at this time we were sitting here thinking about the
regionally severe and earlier flu season. So there is indeed a
demand in the United States. So that takes us into 2004.
In July 2004 our quality assurance programs identified two
consequential batches which failed our standards, and they
turned out to be sterility problems. We then formed a team to
identify the root cause. In late August I was advised that we
would likely be delaying the shipment of Fluvirin relative to
our previous release forecast. We immediately informed both
regulatory agencies, MHRA and the FDA, of the expected delay
and our adjusted forecast of supply. This, incidentally, led to
a press release in August. Since then we have been in regular
consultation with both agencies to update them on the progress
of our confirmatory testing program, and has brought us now to
September 27th.
On September 27th our internal testing program concluded
favorably. We expected, therefore, to be able to supply between
46 and 48 million doses to the United States. We initiated a
process of reporting the outcome of our confirmative testing
program to the regulatory agencies, starting with the MHRA. The
MHRA came to visit our Liverpool facility on September 28th to
both evaluate our confirmative testing findings and to start
what turned out to be a 3-day inspection. When the inspection
was completed on September 30th, we received a one-page list of
observations and we responded to those observations 4 days
later, over the weekend; and that took us to October 4th.
On October 5th the MHRA advised us of their decision to
temporarily suspend our Liverpool plant license. And as a
consequence of that decision, our products that were produced,
that were tested, that were retested could not be and were not
released to the marketplace.
Chairman Tom Davis. Thank you very much.
Mr. Mica.
Mr. Mica. Thank you, Mr. Chairman.
Dr. Klein, thank you for your very succinct and direct
recommendations as to what we need to do to get flu vaccine and
vaccine manufacturing in the United States. You covered
incentives, which were also mentioned by the producer of the
FluMist. You talked about stockpiling a bit. You talked about
two things that I got into; I didn't have a lot of time:
regulatory reform and liability reform.
The other thing, Mr. Chairman, that I think he brought up,
as well, was a meeting of stakeholders. These hearings are nice
and they make nice fare; tomorrow it will be a great headline
to bash the FDA, but it doesn't get flu vaccine or other
vaccines that are essential on the market. But a stakeholders
meeting would be very good, where we had people who actually
manufacture and produce this, maybe with some of the FDA folks.
I think, Mr. Chairman, that would be an excellent
recommendation. And, actually, the Virginia health
representative said that Congress needs to take steps, and we
do need to take steps. We are already into another season.
But you pointed out something, too. I am a fairly ignorant
Member of Congress, as has been pointed out here, but you did
highlight one area that I am not that familiar with, and that
is the difference between regulation of a pharmaceutical and a
vaccine. And maybe it is time, as you pointed out in your
testimony, that we re-examine the regulatory regime we have.
And that may be out of the purview of our committee's
jurisdiction, but it is one of the things that we haven't
looked at, and you might want to address it. You probably share
my ignorance in thinking that liability or the threat of
liability, if we could remove that, would also enhance
manufacturing, but I guess we are both probably at the school
and lacking in knowledge.
But I think you hit the nail on the head, doctor. It is too
bad you are the last witness, but I think everything you
pointed out succinctly, again, directly identifies the problem
and where we need to go. So I thank you for that.
How would you compose a stakeholder conference or meeting?
And I think we should do that sooner rather than later, but
give us your idea so we could do something positive. And
Congress must act, as Dr. Stroube has pointed out.
Dr. Klein. Well, I think your remarks are very appropriate
in the sense that you would like to see action, and you would
like to have knowledgeable people involved; and that would
include not only manufacturers, but purchasers, consumers,
legislators, or legislative staff that would convene a session
that would have contrary proposals as the goal. Then to bring
those proposals to this committee or any other body for review
and potential action. But I think as a citizen without
legislative background, I think we need action, and we want to
propose that be moved forward as expeditiously as possible. And
I think in a way the flu crisis that we have now is an
opportunity to light a fire, because what is coming could be
much worse.
Mr. Mica. And Mr. Pien talked about the pending pandemic.
Dr. Klein. The pandemic flu problem is inevitable. It is
not a question of whether----
Mr. Mica. It is when.
Dr. Klein [continuing]. Is it a question of when.
Mr. Mica. Again, you have to excuse my ignorance; I am not
very knowledgeable about some of the regulatory process. But,
again, the point that you raised about treating vaccines
differently from pharmaceuticals--and, again, I am not an
attorney like some of these folks up here, I am just sort of a
leftover businessman. But the question I would have is, from a
technical standpoint, does FDA have the authority to make those
changes in that regulatory distinction, or is that something
that would require a change in the law?
Dr. Klein. I am not sure, but I think FDA----
Mr. Mica. Oh, another ignorant guy. I am sorry.
Dr. Klein. But I think they do have the regulatory
authority to modify----
Mr. Mica. But I think that is an important question, too,
that we should look at and maybe we need to address.
Thank you, Mr. Chairman.
Dr. Klein. I think they can modify their inspection.
Chairman Tom Davis. Thank you.
Mr. Waxman, you are recognized for 5 minutes.
Mr. Waxman. Thank you very much, Mr. Chairman.
Mr. Pien, when FDA inspected the Liverpool facility in June
2003, the agency found 20 serious areas of concern. We now know
that the inspectors believed that official enforcement action
such as a public warning letter was justified. Had a warning
letter been issued, the agency would have detailed the changes
necessary to fix the problems identified. But a warning letter
was never sent; the inspectors' recommendation was downgraded.
As a result, Chiron never received from FDA a specific list of
changes needed to fix the problems at the June 2003 inspection.
That raises the question of whether Chiron, which was in
the process of taking over the Liverpool facility, really
understood what was needed to resolve these concerns. On June
27, 2003, Chiron wrote to FDA asking for a meeting ``as soon as
possible'' to discuss the company's response to the June 2003
inspection. Would this meeting have been an opportunity for the
company to learn more about what steps were needed to correct
the problems at the facility?
Mr. Pien. Mr. Waxman, as I testified before, the inspection
took place in June 2003, and the Liverpool facility was then
not owned by Chiron, it was known by an English company called
PowderJect. Our board of directors conditioned the acquisition
of the Liverpool facility on what was reported to us to be, by
the people in Liverpool, a satisfactory FDA inspection. I think
that most of the correspondence that arose from that inspection
still had the Evans letterhead on it, which was the name of the
previous owner relative to the Liverpool facility.
Since then, my understanding is that there had been
discussions between our people in Liverpool and the FDA
relating to the observations that they made in 2003, prior to
our taking them over. And as I testified before, Chiron made a
very, very conscious decision that, indeed, we want to
remediate against any past observations of deficiencies, and
that was the reason that we followed through with the
remediation program that went into that facility of $15 million
that was spent in addition to the new facility that I talked
about.
Mr. Waxman. You also, on the same basis, I assume, asked
for the meeting with the FDA, so you could find out what they
knew about the plant that you needed to correct.
Mr. Pien. What I understand, Mr. Waxman, is that those
conversations did take place. The regulatory contact were based
in Liverpool, and those conversations did eventually take
place.
Mr. Waxman. FDA told us that they never followed up with
you. So you have a different view of what happened, that FDA
did followup about the June 2003 inspection?
Mr. Pien. Mr. Waxman, what I understand, what I am told is
that around September or October there was a telephone contact
for our people to understand how best to proceed with the
observations that were made in the June FDA inspection in 2003.
Mr. Waxman. A year later, in June 2004, Chiron wrote FDA
again asking for a full copy of the final inspection report.
While this report does not contain formal recommendations for
action, it does contain a number of specific details, including
some recommendations that are not included in initial lists of
agency observations. Now, according to the FDA staff, this full
inspection report should have been delivered to the company in
September 2003. But because of confusion within the agency, it
was sent 9 months later. I heard that Dr. Crawford even
accepted, in response to a question from Mr. Cummings, that
this was a mistake.
Can you explain the difference in the point of vaccine
manufacturing cycle between September 2003 and June 2004?
Mr. Pien. I have not seen that document, so I am not sure.
I should probably study that document such that I can provide
an intelligent answer.
Mr. Waxman. Well, if you get a chance to do that, we would
welcome your comments for the record.
Mr. Pien. We shall.
Mr. Waxman. Would having the full inspection report 9
months earlier have helped the company understand the FDA's
June 2003 inspection better?
Mr. Pien. Congressman, as I testified just now, I
understand there to have been a contact between our Liverpool-
based people who were charged with the fulfillment of the
remediation against the 2003 inspections, and my understanding
is that contact did take place.
Mr. Waxman. The documents we released today show that FDA's
regulatory approach from June 2003 to October 2004 was to rely
on company representations rather than conduct its own
inspections to make sure the problems were being corrected. For
example, after you announced a problem with contamination in
August 2004, FDA chose to rely on a series of conference calls
with you into October. But this approach did not work. From the
end of August until the British shut the facility, you were
telling FDA and the public that the contaminated vaccine was
limited in amount and you had every expectation that the rest
of the vaccine was on track for this year.
The problem with the FDA approach is when what you said
turned out to be wrong, things were not OK, both British and
FDA inspectors found systemic problems, including failures to
address high bio burdens, problems addressing connection
between tanks and sanitary practices that were found on
previous inspections. So FDA was taken by surprise when the
British came in and found out these problems.
It seems obvious to me if we had known earlier, we could
have planned for the shortage. But, if you know, why did the
company provide FDA with information and projections that
turned out to be wrong; was it deliberate, or would it be fair
to say the company was not aware of the severity of the
problems and was optimistic any problems could be overcome?
Mr. Pien. Congressman Waxman, as I know you know this, the
making of the flu vaccine is a terribly complicated thing; it
is a new product every year, it is actually one product made up
of three components every year. And you start, therefore, with
a very large number of eggs, you put these seeds of viruses
into the eggs and you make it grow, and then you harvest it.
And the process is complex, and that is the reason that you
would have, as a manufacture, these series of procedures for
testing and retesting.
In July 2004, as I testified before, our quality assurance
program identified two batches of products that had sterility
issues, and when that occurred, we thought that the scope of
the problem did not appear to threaten any supply expectations
that we had at the time, and we began to test and do these
programs and investigate what caused it, the so-called root
cause diagnosis and determination. And as you would expect in
making flu vaccines in the way that I have just described--by
the way, at the peak of the production season, one can be
talking about 400,000, 500,000 eggs. So what you alluded to is
the bio burden issue--I think Commissioner Crawford has already
testified--happens. The trick is to make sure that you have a
robust process that, therefore, the end product does not have
any of this bio burden.
Therefore, we expected some failures in these internal
testing programs, and that is why we were performing these
confirmative tests.
Mr. Waxman. You thought they were isolated failures.
Mr. Pien. We did.
Mr. Waxman. But you didn't think they were systemic
problems, which, of course, the FDA report seemed to indicate.
Mr. Pien. We understand that. And as I testified before,
this came to us as a surprise. When it came on October 5th,
when the MHRA had, as previously agreed, come to take a look at
our confirmative testing results, they said they would come;
they came. The day after we finished the testing program they
came and looked at our results and did a 3-day inspection. At
the end of the 3-day inspection we were given one sheet of
paper showing us some of the observations, which we responded
to within 4 days; and the day after that the MHRA concluded
that there are issues with respect to the systems and processes
of the entire plant.
Mr. Waxman. Well, my concern--and I see my time is up--is
that you were taken by surprise, the Food and Drug
Administration was taken by surprise, and yet there had been an
evaluation done in 2003 that showed systemic problems. And I
don't think that the Food and Drug Administration followed
through. They should have been more on the case. You were
taking over the company, and they should have been working with
you together to make sure that these problems were dealt with.
But when you had an increase in production and systemic
problems, it just led to what now looks an inevitable, in
retrospect, breakdown in the system.
Mr. Pien. Mr. Waxman, if I may point out the obvious. We
are in a regulated industry. So if you are asking me to
criticize our regulators, that simply isn't something that I
can do, will do, or shall do. Look, we have a plant. We have a
set of procedures.
Mr. Waxman. Let me interrupt you. I am not asking you to
criticize the regulators. I will do that job, because I think
they deserve criticism. But I think it would be interesting to
know if you had their observations early enough, whether you
could have done something about the problem. And I would submit
that it just makes sense that if you are not told there is a
problem, you may or you may not catch it. But FDA's job should
have been to be on the case to make sure these problems were
dealt with.
Mr. Pien. Mr. Waxman, if I may. Here is our situation now.
We lost our license for this 90-day period. We are trying to
get it back. Now, we are going to do everything we can, that we
can define. Once we define those things that we can, we will do
those things subject to our assessment that we can actually do
them. And I think what is extremely encouraging is that both
the MHRA and the FDA have looked at this issue and this
situation and this experience, and the two agencies, as I
testified before, are working extraordinarily closely. So to
the extent that your observations should inspire some lessons
for all of us going forward, I think that inspiration has
already been achieved.
Mr. Waxman. Well, I thank you for that. That certainly is
what we want, in the future, to have the problems corrected. I
just want to make sure that people understand the mistakes that
were made in the past so that they are never repeated again,
and that we have a regulator that is doing a good job of
regulating, because the purpose of it is to protect the public.
Mr. Pien. We concur.
Chairman Tom Davis. Thank you.
Let me say to my friend, Mr. Waxman, in my opinion, after
listening to everything today, there is no question that had
the FDA gone in early or the MHRA gone in earlier and alerted
them, we might have been able to avert this. But that was not
part of their protocols at the time. I think they followed the
protocols, as I understand it. It doesn't mean they couldn't
have done more, or in the future shouldn't. And I think maybe
one of the lessons coming out of this, particularly for foreign
vaccine manufacturers, we need to be more vigilant and have
more rigid protocols.
Mr. Waxman. If you would just yield to me.
Chairman Tom Davis. Sure.
Mr. Waxman. Their protocols call for what they did, but
they also call for an enforcement letter if it is more serious.
And I would submit that this is not Rogaine, a product which I
didn't use in time. But this is a product that is essential to
the health of millions of Americans to avert the flu and the
consequences for those who are at risk. And there should have
been a higher priority and concern over the flu supply than to
treat it in the same routine way they might treat Rogaine and
other drugs that don't have the consequences of failure in this
case.
Chairman Tom Davis. Well, that is certainly a propecious
comment. But I think FDA and Chiron have basically said to the
committee that the inspection didn't show systematic problems
in 2003.
Is that correct?
Mr. Pien. That is our understanding from the people who
experienced the inspection.
Chairman Tom Davis. And we may have a difference of
interpretation here, but----
Mr. Waxman. Well, we will let the documents that we put out
today speak for themselves.
Chairman Tom Davis. Exactly. And it may be an
interpretation----
Mr. Waxman. Because the FDA inspectors thought otherwise.
Chairman Tom Davis. But I think the testimony is pretty
clear that after they went back, as they do, and examined
these, the biogenics, and they came back and talked about it,
they decided it wasn't. But I think the documents will speak
for themselves. We need to move forward. And I think, Mr.
Waxman, one thing you have contributed very positively today is
the fact that we need to be more vigilant in these areas. And
whatever the protocols were, they need to be tweaked at this
point, as we move forward. We cannot allow this to happen
again. And had we had earlier inspections, not only would
Chiron maybe saved a boatload of money, but we might have had
more vaccine available to people this year.
Let me just ask a few more questions, if I can. I haven't
had my 5 minutes yet.
Mr. Tierney, go ahead. Then I will wrap up. Go ahead.
Mr. Tierney. I don't think I am going to take a full 5
minutes, Mr. Chairman, and I thought you had your 5 before.
Let us segue into looking forward a little bit.
Dr. Coelingh, am I saying that correctly?
Ms. Coelingh. It is Coelingh.
Mr. Tierney. Coelingh. I am sorry. You talked about what we
might do in terms of going forward to make sure that we have
enough vaccine on the market. This, so far, has been an
industry that has been market-driven, as opposed to government-
driven or having government intervene other than the regulatory
process. You talked about seeking tax incentives. Well, that
obviously would take it outside the free market aspect. You
talk about government stimulating demand. That would take it
outside the free market aspect on that. So if industry can't
survive or can't expand in a free market environment, and if
you are going to ask taxpayers then to sort of use their tax
dollars to invest in the industry, either by tax incentives or
by mandatory public purchases, what do you think the industry
would offer back to those taxpayers or investors as
compensation or as a dividend for that? Would they offer up a
share of the profits; would they talk about price controls and
a guaranteed supply; would they talk about tighter safety
regulations; would they talk about contributions, as Dr. Klein
talked about, in terms of a VIP type of situation in case there
is an error or injury to somebody? Would they talk about all of
those or some combination?
Ms. Coelingh. Well, one thing that this industry--I think
that is really misunderstood about how the vaccine, especially
the flu industry vaccine operates, is that it really is
different from a lot of other things where you say a free
market system.
Mr. Tierney. You operate for a profit, right?
Ms. Coelingh. Correct. But what drives this market is the
recommendations of public health authorities. That is the major
driving force in deciding who gets vaccinated and who does not.
Mr. Tierney. Can I just back up for a second? I think what
drives it is individuals that either subscribe to get the
vaccine or they don't, and their decision may be driven by some
comments or decisions that the government makes, right?
Ms. Coelingh. Correct. It is primarily the Advisory
Committee on Immunization Practices. They put out a list of who
should and who should not get vaccine every year. And the
American Academy of Pediatrics and the American Association of
Family Practitioners also follow in step with those
recommendations.
Mr. Tierney. Is that terribly different than companies that
sell things for lowering your cholesterol, where the FDA and
other advisory groups put out a word saying that you ought to
take these medications to lower your cholesterol?
Ms. Coelingh. The main difference is when you are ill and
you need to get a drug to change that situation, it is a lot
different than--most of us are walking around perfectly
healthy, there is nothing wrong with us except influenza will
be coming. So there is an additional----
Mr. Tierney. Well, I am just carrying forward my example.
Most people walking around with high cholesterol are feeling
great and not thinking there is anything imminent there either.
Ms. Coelingh. True. But those medicines are prescribed for
a condition; whereas, we are in the area of preventive
medicine. So there is a higher hurdle to get people to value
influenza prevention and----
Mr. Tierney. Now, other industries would advertise.
Ms. Coelingh. Correct.
Mr. Tierney. Do you?
Ms. Coelingh. Last year was our launch season, 2003, and
during our launch season we did.
Mr. Tierney. I don't mean to tag it all on your company; I
am talking about the industry. So I want to remove that from
anything person on that.
Ms. Coelingh. Yes, there is some advertising. But primarily
what happens is the guidance from the CDC and their advisory
committees tell doctors who gets vaccine and when they get
them.
Mr. Tierney. But the industry could advertise, as other
industries do, if they want to drive a market, right?
Ms. Coelingh. Correct. Absolutely. But how vaccines are
used is not usually driven by direct-to-consumer advertising.
Mr. Tierney. I understand there is some difference on that.
But if you chose, in a free market environment, to advertise to
drive your market, then that would be one way to do it. You are
saying that your industry thinks it better to either have
taxpayer incentives of some sort or public purchases. So my
question that we haven't answered yet, and I would like to get
to, is what would the industry offer back?
Ms. Coelingh. What the industry offers back is new and
improved vaccines that really will change how medicine is
practiced in the United States. We haven't had great changes in
our vaccine industry----
Mr. Tierney. Couldn't we get that just by having NIH do the
research?
Ms. Coelingh. By having, I am sorry?
Mr. Tierney. NIH or some other entity do the research.
Ms. Coelingh. Well, you know, NIH does a great job at doing
research, but they don't make vaccines.
Mr. Tierney. Well, we could either give them the authority
to or establish somebody that does, right?
Ms. Coelingh. Well, that comes at a price as well.
Mr. Tierney. But I guess what you are telling me is the
industry doesn't feel it would owe anything back to the
taxpayers if the taxpayers became their investors.
Ms. Coelingh. I am not saying that we necessarily feel that
the government has to purchase strategic reserves or purchase
unused vaccine. We would much rather make vaccine and have it
used than stockpiled and maybe never used.
Mr. Tierney. But the two things that you did recommend, one
was tax incentives, which would be a taxpayer incentive; the
other was public purchases for school children or whatever.
Ms. Coelingh. It is a universal recommendation for
children.
Mr. Tierney. So, again, why are you putting that burden on
the government for an industry that usually are talking all
about the free market? Why not advertise and take it upon
yourselves to use your investment and your stakeholders'
investments to do that?
Ms. Coelingh. Well, first of all, we have invested alot in
this product, and, second, if the U.S. Government invests in
this product, what they get is they get to not have this kind
of situation happening again.
Mr. Tierney. But there are a number of ways to skin that
cat, right?
Ms. Coelingh. And you get to not have to face the pandemic
without having a vaccine as well. So I think those are things
that are hard to appreciate because you don't worry about them
until they happen, and that is the whole problem with
prevention.
Mr. Tierney. I guess I don't want to drive too fine a point
on this, but let me just drive a real fine point.
Ms. Coelingh. OK.
Mr. Tierney. If we make you fabulously wealthy because you
have all of these new customers or whatever, or you get tax
breaks, why would a taxpayer not expect something back?
Apparently you are not going to answer, and that is fine, but
that would be the question I would have, and I would think a
lot of taxpayers have. If you are going to go out there and
make a profit from the taxpayers' investment one way or the
other, then why wouldn't they get some guarantees back that
would be of value to them.
But thank you for your colloquy.
Chairman Tom Davis. Thank you.
It would probably be cheaper to do it through tax
incentives than direct purchase, but that is an economic
argument that we could get into.
Let me ask each of you a few questions. Let me start, Dr.
Coelingh, with you.
MedImmune right now is looking for universality, is that
correct, in terms of being able to market it to everyone and
getting those protections?
Ms. Coelingh. Correct. We think that is a good solution to
stabilize the market.
Chairman Tom Davis. Oh, it would be a wonderful solution.
You heard the FDA Acting Director today talk about how they
were working toward that. Are we getting satisfaction working
toward that? Is there anything we can do to try to move that
along?
Ms. Coelingh. Well, the Advisory Committee on Immunization
Practices started talking about moving toward a universal
recommendation a couple of years ago, and I think there is a
lot of support amongst the scientific community and the medical
community and the public health community. I think there is a
desire to want to do that because we appreciate what could be
accomplished by those means. However, I think it comes down to
it is going to have to be supported by a lot of education for
people to understand, No. 1, why is influenza a problem,
because often it is thought of as just a minor cold. We don't
realize that 36,000 people die in the United States every year
from complications due to influenza and another 200,000 are
hospitalized every year. Look at the cost of that to our
society. So I think we need to educate people so that they
understand how important it is to protect our citizens.
Chairman Tom Davis. You also, in your particular product,
are trying to make sure that this would immunize older patients
and younger patients. There is no evidence that it doesn't, it
is just that the burden of proof is on you to show that it
does, is that correct?
Ms. Coelingh. We are trying to expand our indication down
lower, below the age of 5.
Chairman Tom Davis. And higher.
Ms. Coelingh. And higher. So we have recently submitted new
analyses of data that we have to show that the product is
effective in adults from 50 to 64 years of age, and the FDA
should be reviewing that soon.
Chairman Tom Davis. Where is your plant?
Ms. Coelingh. Well, our manufacturing is done in three
stages. The first stage is manufacturing of the seed viruses,
which Mr. Pien has referred to; and we do that in northern
California, in the Bay Area. So the seeds are made there. Then
those are shipped to Liverpool and our bulk manufacturing is
done there. And then the bulks are shipped to our Philadelphia
plant and they are blended and filled into the nasal sprayers.
Chairman Tom Davis. These are global viruses, then, as they
move through. Well, thank you very much. We appreciate
everything that you are doing.
Mr. Pien, let me ask, the suspension of your license hasn't
prevented you from procuring the materials necessary to move
forward next year. You are planning as if you are going to go
full boat, correct?
Mr. Pien. What we are doing is we are defining all of the
details of the implementation to achieve remediation, and it is
going to take stages, and the first stage is to get the MHRA to
come back into our plant, probably in December, to look at
whether or not they are going to be able to allow the 3-month
suspension of license to expire.
Chairman Tom Davis. But you have the eggs lined up and
everything as if you are ready to go, right?
Mr. Pien. Yes.
Chairman Tom Davis. And, in fact, if you don't get
licensed, you are stuck with a lot of eggs. You will be in the
chicken business, won't you?
Mr. Pien. Well, we will be in a different business than
vaccines, yes.
Chairman Tom Davis. So we appreciate that is a considerable
risk for your coming, just moving ahead in a case like that.
Mr. Pien. We recognize that.
Chairman Tom Davis. And I think we appreciate and I think
it shows the can-do attitude here as we move forward, but I
just wanted to point that out. You feel encouraged in your work
is that fair to say, with MHRA and the FDA, to ensure that you
will be able to manufacture for next year?
Mr. Pien. We feel encouraged in the approach that I have
outlined in my testimony has received considerable positive and
constructive feedback from both the MHRA and the FDA.
Chairman Tom Davis. The issues that were identified that
led to the suspension of the license were not facility issues,
were they? Weren't there more management issues, human factors
issues?
Mr. Pien. Chairman Davis, that is largely correct. The MHRA
did make some recommendations as to whether or not this machine
should be here and that machine should be there, and also made
some observations about our quality control system and testing
program. All of those things are in the scope of our
remediation plan proposal.
Chairman Tom Davis. And let me just say for the record we
met with the FDA and we met with the MHRA, and everybody
working together on this felt pretty good about where we are
going, but, as you said, there are no guarantees in this
business.
Mr. Pien. No guarantees, first of all, but absolutely. And
I think everybody has heard Mr. Waxman's suggestions about
learning from our mistakes.
Chairman Tom Davis. I have heard a lot of them here too.
Dr. Stroube, how is Virginia doing at this point? Is the
CDC making sure we are getting enough to take care of our
vulnerable population?
Dr. Stroube. We are getting our fair share; they are
allocating it by population. And with this new data base and
today triggering the ordering thing, ordering part of it, we
will be able to do the best we can with the limited vaccine
that is available.
Chairman Tom Davis. How is the vaccine dosage distribution
information on the Flu Vaccine Finder working? It is only
available to State health officials. Is that working
satisfactory, from your perspective?
Dr. Stroube. Yes. It is getting better. Like I said, they
upgraded it this morning before I left, and I played with it
some, where you can go in and actually now we can approve the
ordering of vaccine and direct where it goes to on that system
through the distribution and through Aventis.
Chairman Tom Davis. You notice some other States have gone
out and gone to other foreign manufacturers that are not
licensed by FDA, but FDA, we heard today, is looking at trying
to give them some certification so that they can bring it in.
Has Virginia given any thought to doing that?
Dr. Stroube. We have talked it over, but we have not done
that.
Chairman Tom Davis. You think you can get an adequate
supply for the vulnerable population without doing that?
Dr. Stroube. Well, we were worried about the timeliness
since we were working with what we have to get it out, because
we were really worried. We have had some cases in nursing homes
already, so we went ahead and used some of the vaccine that we
already had gotten for the public health side and just diverted
it right away to the nursing homes to try to get them
protected. So we have been working with what we had, and with
the expectation a foreign vaccine does get approved, it will be
put through the CDC system, as I understand it, the same way,
and we should get a share of the 5 million that FDA is working
on.
Chairman Tom Davis. Thank you.
Dr. Klein, current flu vaccine recommendations cover people
under the age of 2 and over 50 to include people who have
underlying medical conditions and put them at high risk. Do you
think the current flu vaccine recommendations are adequate, or
should they be expanded to recommend it for all Americans?
Dr. Klein. I think the group is at risk, those that have
been targeted and those that had the highest hospitalization
rates, the most morbidity, and the elderly, the mortality, but
I think it is a matter of cost-benefit for employers who have
employees who may have to miss work. Certainly we make it a
matter of importance that all health personnel be immunized so
not only do they stay on the job during an outbreak, but they
don't pass on the virus to their patients. And I think the same
arguments could be made in almost every venue, that the
importance in preventing disease, in this case respiratory
disease, does have a cost-benefit and would be beneficial to
all ages.
Chairman Tom Davis. So an ounce of prevention is worth a
pound of cure.
Dr. Klein. It will be exam times; college students should
be protected.
Chairman Tom Davis. Would a universal flu vaccine
recommendation also help ensure a stable flu vaccine supply?
Dr. Klein. I think so, in the sense that one of the goals,
I think, of any program that addresses these issues should be
to engage additional manufacturers, particularly domestic
manufacturers, and if they have guaranteed market with some
price structure that makes it profitable, I think they will
return to the market and make that vaccine available. And then
there will be flexibility, so that if there is a problem with
one manufacturer, it will influence modestly the vaccine
supply.
Chairman Tom Davis. You all have heard everybody's
testimony today, the first panel with the FDA and the CDC and
everyone else. Are we missing anything here? Is there anything
else we ought to be doing that hasn't been discussed or
recommended?
Dr. Klein. No, but I hope the various authorities, bodies
of importance, direct long-term measures, not just to put out
this fire, but to consider that this probably will occur in the
future; that vaccine shortages have taken place in the past,
the current one is important, and they will take place in the
future unless we build in some new safeguards against that. But
that will take a lot of perseverence and continued interest.
Chairman Tom Davis. Thank you.
I would ask unanimous consent that the three statements
previously submitted to the committee be entered into the
record. Without objection, so ordered.
Mr. Waxman, do you have any followup questions?
Mr. Waxman. I do, Mr. Chairman. It is interesting to take
note of the fact that we have a crisis right now; we have an
inadequate supply for the flu season for the vaccinations.
Yesterday a committee of the Senate held a hearing; today this
committee is holding a hearing; tomorrow there will be another
committee in Congress holding a hearing, it is a subcommittee
over in the Energy and Commerce Committee. Obviously, Congress
cares a lot about this issue, appropriately so. We want to
learn from our mistakes.
But I want to ask you, Dr. Klein. You are one of the
leading experts in childhood infections and you served on the
National Vaccine Advisory Committee. We are acting as if this
has never been an issue, that suddenly we have a whole issue of
vaccine supply and we never imagined we would have such an
issue before us. Didn't the Advisory Committee present a report
in October 2002?
Dr. Klein. It did, and many of the issues that I addressed
are those that have been partially addressed, such as there was
additional funding made available for vaccine stockpile. But
because of the SEC regulation, that hasn't been implemented.
But the others, because they are complex and they require
perseverence, have been managed in a stop gap measure. And we
need to reinstitute a more durable set of advisory groups that
will be able to address and propose specific recommendations
that can alleviate the long-term problems.
Mr. Waxman. So before October 2002, your Advisory Committee
was looking at the issue of how to give the right incentives
for manufacturers to want to invest in producing vaccine, to
make sure that they would have a sufficient supply, that the
unsold batches wouldn't be a disincentive for them, for
example. So the recommendations were made to set up a committee
to look at and give further thoughts to it, is that what
happened in October 2002?
Dr. Klein. Well, actually, the workshop was in February
2002, and as a result of that there was an IOM report of
financing vaccines that was issued, but it in itself wasn't
complete or wasn't sufficiently complete, and was somewhat
controversial. So you need continuing activity to maintain
until proposals that are satisfactory can be given to this
committee and others.
Mr. Waxman. So the Vaccine Advisory Committee proposed a
multi-disciplinary committee to be operating on an ongoing
basis to address these issues of vaccine supply.
Dr. Klein. That is correct.
Mr. Waxman. Now, what happened to that recommendation, was
it adopted?
Dr. Klein. The recommendation for the ongoing----
Mr. Waxman. Yes.
Dr. Klein. The IOM report was issued in the latter part of
2003. In June 2004 there was an NVAC meeting that was
specifically held to continue that dialog, and we are
interested now in progressing further so that something can be
done. But the Vaccine Advisory Committee is just that, it is
advisory to the National Immunization Program and the Assistant
Secretary of Health and Human Services.
Mr. Waxman. Well, we need the advice from the experts, and
we had an advisory committee who gave us recommendations; we
had the Institute of Medicine give us recommendations. But from
what I can tell, none of these recommendations have been
followed up on, especially in this area, where everybody is now
for giving incentives for production of vaccine so we won't
lose supply and face the problem we are facing now. Even
Secretary Thompson seems to be talking about the importance of
financial incentives.
The point I want to make is we shouldn't wait for a crisis.
We have advisory committees. In fact, your testimony here today
is helpful, but it is advisory to us in many ways to have
Congress act. And if Congress only holds a hearing while there
is attention paid to the issue, and if the Secretary of Health
and Human Services only pays a high priority to this issue when
there is a crisis, and when there is no crisis it is pushed
aside, it is inevitable we are going to come back and repeat
the same mistakes over and over again.
Let me just ask you parenthetically, because you know this
issue very well. Is liability a strong disincentive for the
manufacturing of flu vaccine?
Dr. Klein. No, it is not.
Mr. Waxman. It is not? Why not?
Dr. Klein. The flu vaccine, for the most part, has been a
very safe product; it is made in eggs, so anybody with an egg
allergy would be excluded from getting the vaccine. And there
have been minor problems in the past. There was one experience
with swine flu, where there was a neurologic disability that
followed. And there are a couple of minor issues that occurred.
But the reason for this current shortage is not liability, it
is associated with a problem that Chiron experienced. That
there are ingenious ways of getting around the current
legislation and the Vaccine Injury Compensation Program is a
given, and that is why that program needs to be reviewed
constantly and assured that it remains as strong as it has been
in helping the administration of vaccine, those who administer
vaccines, as well as the manufacturers, be clear of liability
for approved vaccines.
Mr. Waxman. Well, I think you are absolutely right on that,
and I hope we will get to--not on this committee, but on the
committee that has jurisdiction, although this committee did
come up with some recommendations on the Vaccine Compensation
Program.
Mr. Chairman, I want to thank you for holding this hearing,
and thank all the witnesses for their testimony. I hope we can
learn from this experience that we are facing now to do things
better and to learn from our mistakes, and hope that we don't
make the same mistakes again, and the ones we do won't have the
catastrophic consequences that we seem to be facing with so
many at-risk people having flu vaccine completely unavailable
to them.
Chairman Tom Davis. Well, let me thank this panel not just
for testifying here today and sharing your views, but what you
are doing outside of this hearing room, trying to get more
vaccines to people in need. Thank you very much.
The hearing is adjourned.
[Whereupon, at 4:55 p.m., the committee was adjourned.]
[The prepared statements of Hon. Christopher Shays, Hon.
Tom Lantos, Hon. Major R. Owens, Hon. Edolphus Towns, Hon.
Carolyn Maloney, Hon. Elijah E. Cummings, Hon. Dennis J.
Kucinich, Hon. Diane E. Watson, and Hon. Michael C. Burgess,
and additional information submitted for the hearing record
follow:]
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