U.S.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
CENTER
FOR BIOLOGICS EVALUATION AND RESEARCH
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VACCINES AND RELATED BIOLOGICAL PRODUCTS
ADVISORY COMMITTEE
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97TH MEETING
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WEDNESDAY,
FEBRUARY 18, 2004
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The Advisory Committee met at 8:30 a.m. in
the Embassy Room of the Sheraton Four‑Points
Hotel,
8400 Wisconsin Avenue, Bethesda, Maryland, DR.
GARY
OVERTURF, Chairman, presiding.
This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly the Food & Drug Admin. Makes no representation as to its accuracy.
PRESENT:
GARY D. OVERTURF, M.D.
MICHAEL D. DECKER, M.D.
MONICA M. FARLEY, M.D.
RUTH A. KARRON, M.D.
PHILIP S. LaRUSSA, Ph.D.
DAVID MARKOVITZ, M.D.
PETER PALESE, Ph.D.
CINDY LYN PROVINCE
WILLIAM FREAS, Ph.D.
I‑N‑D‑E‑X
AGENDA ITEM PAGE
Call to Order, Dr. Gary Overturf, Chair 9
Administrative Matters, Dr. Bill Freas 3
Presentation of Plaques to Retiring 9
Members, Dr. Karen Midthun
OPEN Session 11
Strain Selection for Influenza Virus 11
Vaccine for the 2004‑2005 Season
Introduction, Dr. Roland Levandowski, FDA 11
Vaccine Effectiveness, Dr. Carolyn 61
Bridges, CDC
Col. James Neville, DOD
90
Dr. Antoine Flahault, INSERM, Paris
104
U.S.
Surveillance, Ann Moen, CDC
118
Open Public Hearing
World Surveillance and Strain
Characterization, Dr. Nancy Cox, CDC 139
Additional Reports, Linda Canas, DOD
Dr. Maria Zambon, HPA, UK
176
Vaccine Responses,
Dr.
Roland Levandowski, FDA
195
Availability of Strains and Reagents, 216
Dr.
Zhiping Ye, FDA
Comments from Manufacturers 220
Update on H5, Dr. Nancy Cox, CDC 241
Dr.
Phil Minor, NIBSC
262
NIH
Speaker (TBA)
Adjourn 300
P‑R‑O‑C‑E‑E‑D‑I‑N‑G‑S
(8:37 a.m.)
ADMINISTRATIVE MATTERS
MEMBER FREAS: Mr. Chairman,
members of
the Committee, invited speakers, and members of
the
public, I would like to welcome all of you to
this,
our 97th meeting of the Vaccines and Related
Biological Products Advisory Committee meeting.
I am Bill Freas. I am the Acting
Executive Secretary for today. At this time, before
the meeting, begins, I would like to go around
and
introduce to the public the members seated at the
head
table.
We will start on the right side of the
table.
That is the audience's right‑hand side. And
I will read the names of the people at the table.
Would the members please raise their hands as I
call
their names?
David Markovitz, Professor, Division of
Infectious Diseases, University of Michigan
Medical
Center.
Next is Dr. Walter Dowdle, Senior Public
Health Consultant, The Task Force for Child
Survival
and Development.
Next is Dr. Judith Goldberg, Director,
Division of Biostatistics, New York University
School
of Medicine.
Next is Dr. Ruth Karron, Associate
Professor, Johns Hopkins School of Hygiene and
Public
Health.
Next is Dr. Walter Royal, Associate
Professor of Medicine, Morehouse School of
Medicine.
Next is Dr. Monica Farley, Professor of
Medicine, Emory University School of Medicine.
Next is Dr. Pamela McInnes, Deputy
Director, Division of Microbiology and Infectious
Diseases, NIH.
Next is Ms. Cindy Lyn Province, Associate
Director, Bioethics Center of St. Louis.
Next is Dr. Bruce Gellin, Director,
National Vaccine Program.
In the empty chair, we will soon be joined
by Dr. Stephen Phillips, Director, Deployment
Medicine
and Surveillance, Office of Assistant Secretary
of
Defense.
Next I would like to introduce you to the
Chair of this Committee, Dr. Gary Overturf,
Professor
of Medicine, University of New Mexico School of
Medicine.
Coming around the table, we have Dr.
Philip LaRussa, Professor of Clinical Pediatrics,
Columbia‑Presbyterian Hospital.
Next we have Dr. Martin Myers,
Co‑Director, Public Health Policy and
Education,
University of Texas Medical Branch.
Next we have Dr. Bonnie Word, Assistant
Professor of Pediatrics, Baylor College of
Medicine.
Next we have Dr. Peter Palese, Chairman
and Professor, Department of Microbiology, Mt.
Sinai
School of Medicine.
Next we have Dr. Arnold Monto, Professor,
The University of Michigan.
Next we have Dr. Ted Eickhoff, Professor
of Medicine, University of Colorado Health
Sciences
Center.
Next we have our nonvoting industry
representative, Dr. Michael Decker, Vice President,
Scientific and Medical Affairs of Aventis
Pasteur.
Next we have a nonvoting participant, Dr.
Nancy Cox, Chief of the Influenza Branch, Centers
for
Disease Control and Prevention.
Next we have Dr. Roland Levandowski from
the FDA.
Dr. Richard Whitley, University of
Alabama, member of this Committee, has recused
himself
from today's participation.
I would like to thank the members for
attending.
There is one other person I would like to
introduce at this time. Many people have asked me,
"When are you going to get a real executive
secretary
for this Advisory Committee?" I would like to
introduce this morning Christine Walsh, who will
be
the next Executive Secretary for this Committee
at the
next meeting, which will be announced later. It will
be either in March or May. We have a teleconference
scheduled for March the 17th at this time.
I would now like to read the conflict of
interest statement into the record. Before I do that,
I would like to ask the members of the public if
they
could put their cell phones on silence mode, it
would
be appreciated.
"The following announcement addresses the
conflict of interest issues associated with the
Vaccines and Related Biological Products Advisory
Committee meeting on February 18th and 19th,
2004.
The Director of the Center of Biologics
Evaluation and
Research has appointed Drs. Walter Dowdle, Ted
Eickhoff, Bruce Gellin, Judith Goldberg, Pamela
McInnes, Arnold Monto, Martin Myers, and Stephen
Phillips as temporary voting members for this
meeting.
"Based on the agenda, it has been
determined that there are no specific products
being
approved at this meeting. The Committee participants
have been screened for their financial
interests. To
determine if any conflicts of interest existed,
the
agency reviewed the agenda and all relevant
financial
interests reported by the meeting participants.
"The Food and Drug Administration prepared
general matters waivers for participants who
required
a waiver under 18 U.S. Code 208. Because general
topics impact on many entities, it is not prudent
to
recite all potential conflicts of interest as
they
apply to each member. FDA acknowledges that there may
be potential conflicts of interest, but because
of the
general nature of the discussions before the
Committee, these potential conflicts of interest
are
mitigated.
"We would like to note for the record that
Dr. Michael Decker is a nonvoting industry
representative for this Committee acting on
behalf of
a regulated industry. Dr. Decker's appointment is not
subject to 18 U.S. Code 208. He is employed by
Aventis and, thus, has a financial interest in
his
employer.
In addition, in the interest of fairness,
FDA is disclosing that his employer, Aventis, is
a
manufacturer of a product that could be affected
by
today's discussions.
"With regards to FDA's invited guest
speakers, the agency has determined that the
services
of these speakers are essential. The following
interests are being made public to allow meeting
participants to objectively evaluate any
presentation
and/or comment made by the speakers.
"Dr. Antoine Flahault is employed by the
World Health Organization Collaborating Center
for
Electronic Disease Surveillance in France. He has
associations with firms that could be affected by
the
Committee discussion.
"Dr. Maria Zambon is employed by the
Respiratory Virus Unit, Health Protection Agency
in
England.
Her agency's laboratory conducts tests on
licensed influenza vaccines. Her employers
collaborates with firms that could be affected by
the
Committee discussions.
"In addition, there are vaccine
manufacturers making industry presentations. These
speakers have financial interests associated with
their employer and with other regulated
firms. They
were not screened for conflict of interest.
"Members and consultants are aware of the
need to exclude themselves from the discussions
involving specific products or firms for which
they
have not been screened for conflict of interest.
Their exclusion will be noted in the public
record.
"With respect to all other meeting
participants, we ask in the interest of fairness
that
you address any current or previous financial
involvement with any firm or product you wish to
comment upon.
Waivers are available by written
request under the Freedom of Information
Act."
So ends the reading of the conflicts of
interest statement. Dr. Overturf, I turn the meeting
over to you.
CALL TO ORDER
CHAIRMAN OVERTURF: Good
morning. I would
like to welcome everybody to this meeting of the
VRBPAC Advisory Committee February 18th and 19th.
Dr. Midthun, would you like to make
presentations to retiring members?
PRESENTATION OF PLAQUES TO RETIRING MEMBERS
DR. MIDTHUN: Good morning. I would like
to ask Dr. Judith Goldberg to please come up to
the
podium. I
would like to thank her for her many years
of service on this Advisory Committee. She has always
been here with great dedication, always has
prepared
extremely well, and provided excellent input to
us.
We are really going to miss her and really
appreciate
all that she has given to us.
I think I am supposed to stand over here
so we can get with the picture of the
plaque. Thank
you. And
we also have a letter here for you from Mr.
Peter Pitts, who is our Associate Commissioner
for
External Relations. So thank you so much.
(Applause.)
DR. GOLDBERG: I just want to thank all of
you because it has really been a privilege to
serve on
this Committee.
I have enjoyed every minute of it,
and I have learned a tremendous amount.
DR. MIDTHUN: Thank you so much.
CHAIRMAN OVERTURF: I think we
will
proceed.
As you know, there has been a great deal of
interest in influenza, for those of you who
forgot
about last winter. So this year I think will be a
striking update of last year. So that I think we will
begin with the data that is going to be presented
by
Dr. Roland Levandowski and his associates. Thank you.
DR. LEVANDOWSKI: Great. Thanks very
much, Dr. Overturf.
OPEN SESSION
STRAIN
SELECTION FOR INFLUENZA VIRUS VACCINE
FOR THE 2004‑2005 SEASON
INTRODUCTION
DR. LEVANDOWSKI: I am going to
try to
give a somewhat extended review of what has been
happening this last season. Generally I do give a
fairly brief review, but today I am going to be
going
into a little bit more detail.
There is an awful lot that is going on.
What we would like to try to cover, just as a
reminder, the real business for today is what is
first
on this list of topics for us to take a look
at. We
are really here today to make the recommendations
for
the strains that should be used in next year's
trivalent vaccine, for the 2004‑2005
trivalent vaccine
for the H1N1, H3N2, and Influenza B viruses.
We do also on this program, as you will
see from the agenda, have some other items that
we
wanted to bring to the attention of the
Committee. In
particular, there are some items that we have
that we
would like to bring to the attention of the
Committee
just mainly for information for things that are
happening.
There has been a lot of interest this year
about the effectiveness of vaccines. This has been a
discussion point at this Committee on many
occasions
in the past.
In fact, I can't remember one when it
hasn't been discussed in recent memory of mine.
So we have several speakers: Dr.
Carolyn
Bridges from CDC, Col. James Neville from the
Department of Defense, and Dr. Antoine Flahault
from
the Institut National de la Sante et de la
Recherche
Medicale, who will be talking about some studies
that
they have ongoing to look at vaccine
effectiveness.
Some of these are still in progress, but we will
at
least get to hear what is happening to try to
look at
this in an ongoing manner.
I also wanted to bring to the attention of
the Committee what is happening with H5 avian
influenza in Asia. At this time last year, you might
remember we were talking about what is happening
with
SARS. So
we know that the Committee will be very
interested to hear this information. We also want to
bring it to the attention of the Committee
because
there may need to be some activities that go on
at a
later date.
We just wanted to have them informed as
much as we can at this point.
Finally, on the agenda, we have something
that we would like to have some discussion with
the
Committee.
This relates to a point that was brought
up last year about use of tissue culture isolates
from
field laboratories for preparation of influenza
vaccines.
You will see on the agenda that tomorrow
toward the conclusion of the meeting we have a
couple
of presentations by one of my colleagues, Zhiping
Ye,
Center for Biologics, and also Dr. Phil Minor
from
NIBSC, to talk about our perspectives on what the
issues might be with issue of tissue culture
isolates.
So this is the main business.
Again, this
is the question that we are asking the Committee
to
give us recommendations today. We are asking for a
vote on this.
This is the abbreviated version of the
question, what strain should be recommended for
the
antigenic composition of the 2004‑2005
influenza virus
vaccine for use in the United States?
Just by way of review, this was the
recommendation that was made by the Committee
last
year at this time. It was for a trivalent vaccine
that would contain an A/New Caledonia/20/99 H1N1‑like
strain.
Actually, it was A/New Caledonia/20/99.
It would also contain a B/Hong
Kong/330/01‑like strain. And in our case, the strains
that were used for vaccine preparation were the
actual
strain, B/Hong Kong/330/2001 or B/Hong
Kong/1434/2002.
The H3N2 component that was recommended based on
all
of the information was for an A/Panama/2007/99‑like
strain.
Why do we change strains for influenza
vaccines?
Well, we do it because the vaccine efficacy
is really related to two things. One is how much
antigen is present in the vaccine and then, very
importantly, what the match of the vaccine,
hemagglutinin and neuraminidase, are with the
wild
type circulating strains. This has been very clear to
us since the earliest days of influenza vaccine
use.
You might remember that influenza viruses
were first isolated in the mid '30s, human
influenza
viruses, mid '30s to early '40s. And it was very