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