1
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
FOOD AND DRUG
ADMINISTRATION
CENTER FOR DRUG EVALUATION AND
RESEARCH
PEDIATRIC ADVISORY
SUBCOMMITTEE OF THE
ANTI-INFECTIVE DRUGS ADVISORY
COMMITTEE
Tuesday, February 3,
2004
9:00 a.m.
Advisors and Consultants Staff
Conference Room
5630 Fishers Lane
Rockville, Maryland
2
PARTICIPANTS
P. Joan Chesney, M.D., Chair
Thomas H. Perez, MPH, Executive Secretary
SGE CONSULTANTS (VOTING):
Mark Hudak, M.D.
David Danford, M.D.
Richard Gorman, M.D., FAAP
Robert Nelson, M.D., Ph.D.
Susan Fuchs, M.D.
Robert Fink, M.D.
Victor Santana, M.D.
Norman Fost, M.D., MPH
Judith O'Fallon, Ph.D.
Ralph D'Agostino, Ph.D.
Mark Fogel, M.D.
Tal Geva, M.D.
Craig Sable, M.D.
Vasken Dilsizian, M.D.
Marilyn Siegel, M.D.
Phillip Moore, M.D.
MEMBERS (VOTING):
Mary Glode, M.D.
Steven Ebert, Pharm.D. (Consumer
Representative)
FEDERAL EMPLOYEE (VOTING):
Mario Stylianou, Ph.D.
INDUSTRY REPRESENTATIVE:
Samuel Maldonado, M.D.
FDA:
Shirley Murphy, M.D.
Solomon Iyasu, M.D.
Hari Sachs, M.D.
Julie Beitz, M.D.
Sally Loewke, M.D.
Shavhree Buckley, M.D.
3
C O N T E N T S
Call to Order and Introductions,
Joan P. Chesney, M.D., 5
Meeting Statement, Thomas H. Perez,
M.P.H.,
Executive Secretary 8
Welcome, Rosemary Roberts, M.D., Office
of
Counterterrorism and Pediatric Drug
Development 11
Adverse Event Reports Per Section 17 of
BPCA,
Solomon Iyasu, M.D., Division of
Pediatric
Drug Development 12
Use of Imaging Drugs in Conjunction
with Cardiac
Imaging Procedures in the Pediatric
Population:
Pediatric Regulatory Update, Susan
Cummins, M.D.,
Division of Pediatric Drug
Development 58
FDA Perspective, Sally Loewke, M.D.,
Division of
Medical Imaging and
Radiopharmaceutical Drug
Products 73
American Academy of Pediatrics
Perspective,
John Ring, M.D., University of
Tennessee
Health Science Center 91
Cardiologist Perspective, Tel Geva, M.D.,
Children's Hospital Boston 106
Q&A for Speakers 126
Contrast Enhanced Magnetic Resonance
Imaging,
Mark Fogel, M.D., The Children's
Hospital
Philadelphia 143
Contrast Enhanced Cardiac Computed
Tomography,
Marilyn Siegel, M.D., Washington
University
School of Medicine 172
Contrast Enhanced Invasive Cardiac
Imaging,
Phillip Moore, M.D., UCSF Children's
Hospital 174
Contrast Enhanced Cardiac Ultrasound,
Craig Sable,
M.D., Children's National Medical
Center 213
Radiopharmaceuticals in Nuclear Cardiac
Imaging,
Vasken Dilsizian, M.D., University of
Maryland
School of Medicine 234
Q&A for Speakers 253
4
C O N T E N T S (Continued)
Open Public Hearing:
Michael J. Gelfand, M.D., Children's
Hospital,
Cincinnati 296
Manuel D. Cerqueira, M.D.,
American Society of Nuclear
Cardiology 311
Peter Gardiner, MB ChB, MRCP,
Bristol-Myers Squibb 316
Jack Rychik, M.D., American Society of
Echocardiography 320
5
1 P R O C E E D I N G S
2 Call to Order and
Introductions
3
DR. CHESNEY: Good morning and
welcome to
4
what should be a very fascinating day and a half.
5 I
would like to start by saying that there is the
6
potential for us to finish our work today if we
7
stay very focused and very attentive to the
8
specific issues that the FDA is asking us to
9
address. But first we need to
have the
10
introductions and I think maybe we could start with
11 Dr.
Maldonado and go around this way, please.
12
DR. MALDONADO: Samuel Maldonado,
from
13
Johnson & Johnson.
14
DR. MOORE: Phillip Moore, from
the
15 University of California San Francisco,
pediatric
16
cardiology.
17
DR. SIEGEL: Marilyn Siegel, from
18
Washington University in St. Louis, pediatric
19
radiologist.
20
DR. DILSIZIAN: Vasken Dilsizian,
21
University of Maryland, Director of Nuclear
22
Cardiology, both adult and cardiology and nuclear
23
medicine.
24
DR. SABLE: Craig Sable,
Children's
25
National Medical Center in Washington, Director of
6
1
Echocardiography.
2
DR. GEVA: Tel Geva, Department of
3
Cardiology at Children's Hospital in Boston.
4
DR. D'AGOSTINO: Ralph D'Agostino,
Boston
5
University, statistician.
6
DR. FOGEL: Mark Fogel, pediatric
7
cardiology, Children's Hospital, Philadelphia.
8
DR. SANTANA: Victor Santana,
pediatric
9
hematologist, oncologist at St. Jude's Children's
10
Research Hospital in Memphis, Tennessee.
11
DR. GORMAN: Rich Gorman,
pediatrician,
12
private practice, Ellicott City, Maryland.
13
DR. EBERT: Steve Ebert,
infectious
14
disease pharmacist, Meriter Hospital, Professor of
15
Pharmacy, University of Wisconsin, Madison.
16
MR. PEREZ: Tom Perez, executive
secretary
17 to
this meeting.
18
DR. CHESNEY: Joan Chesney,
Professor of
19
Pediatrics at the University of Tennessee in
20
Memphis and also at St. Jude's Children's Research
21
Hospital.
22
DR. FOST: Norm Fost, Professor of
23
Pediatrics and Director of the Beioethics Program
24 at
the University of Wisconsin, Madison.
25
DR. NELSON: Robert Nelson,
Critical Care
7
1
Medicine, Children's Hospital, Philadelphia.
2
DR. FINK: Bob Fink, pediatric
3
pulmanology, Professor of Pediatrics, Children's
4
Medical Center, Dayton, Ohio.
5
DR. O'FALLON: Judith O'Fallon,
6
biostatistician, recently retired from the Mayo
7
Clinic.
8
DR. FUCHS: Susan Fuchs, pediatric
9
emergency medicine, Children's Memorial Hospital,
10
Chicago.
11
DR. DANFORD: Dave Danford,
Professor of
12
Pediatrics, Section of Cardiology, University of
13
Nebraska Medical Center and Crayton University in
14
Omaha.
15
DR. GLODE: Mimi Glode, pediatric
16
infectious disease at Children's Hospital,
17
University of Colorado in Denver.
18
DR. HUDAK: Mark Hudak, Professor
of
19
Pediatrics and Neonatology, University of Florida,
20
Jacksonville.
21
DR. SACHS: Hari Sachs, Professor
of
22
Pediatrics and medical officer at FDA.
23
DR. IYASU: Solomon Iyasu. I am team
24
leader at the FDA.
25
DR. S. MURPHY: Shirley Murphy,
the "other
8
1
Murphy." I am the Director
of the Division of
2
Pediatric Drug Development and I am going to be
3
sitting here today because the "other Murphy" may
4
have to deal with counterterrorism.
5
DR. CHESNEY: Thank you and we
6
particularly welcome our cardiology and imaging
7
consultants so that we have some expertise on the
8
committee. We are going to be
very dependent on
9 you
to talk to us about degrading nuclear particles
10 and
so on in the major session for this morning.
11 But
next we would like Tom to give us the meeting
12
statement, please.
13 Meeting Statement
14
MR. PEREZ: Thank you. The following
15
announcement addresses the issue of conflict of
16
interest with respect to Section 17, Best
17
Pharmaceuticals for Children Act Adverse Event
18
Reporting, and is made a part of the record to
19
preclude even the appearance of such at this
20
meeting.
21
This morning you will hear from Dr.
22
Solomon Iyasu, lead medical officer with the
23
Division of Pediatric Development.
As mandated in
24 the
Best Pharmaceuticals for Children Act, Dr.
25
Iyasu will report on adverse events for the
9
1
following drugs that were granted market
2
exclusivity under 505(a) under the Federal Food,
3
Drug and Cosmetic Act, Paxil, paroxetine; Celexa,
4
citalopram; Pravachol, pravastatin and Navebjne,
5
vinorelbine.
6
Because the agency is not seeking advice
7 or
recommendations from the subcommittee with
8
respect to these products there is no potential for
9 an
actual or apparent conflict of interest.
10
The following announcement addresses the
11
issue of conflict of interest with respect to the
12 use
of imaging drugs in conjunction with cardiac
13
imaging procedures in the pediatric population and
14 is
made a part of the record to preclude even the
15
appearance of such at this meeting.
Based on the
16
agenda, it has been determined that the topics of
17
today's meeting are issues of broad applicability.
18
Unlike issues before a committee in which a
19
particular firm's product is discussed, issues of
20
broader applicability involve many sponsors and
21
their products. All subcommittee
participants have
22
been screened for their financial interests as they
23 may
apply to products and companies that could be
24
affected by the subcommittee's discussions of
25
imaging drugs used in conjunction with cardiac
10
1
imaging procedures in pediatric populations.
2
To determine if any conflicts of interest
3
existed, the agency has reviewed the agenda and all
4
relevant financial interests reported by the
5
meeting participants. Based on
this review, it has
6
been determined that there is no potential for an
7
actual or apparent conflict of interest at this
8
meeting.
9
With respect to FDA's invited industry
10
representative, we would like to disclose that Dr.
11
Samuel Maldonado is participating in this meeting
12 as
an industry representative acting on behalf of
13
regulated industry. Dr. Maldonado
is employed by
14
Johnson & Johnson.
15
In the event that the discussions involve
16 any
other products or firms not already on the
17
agenda for which FDA participants have a financial
18
interest, the participant's involvement and
19
exclusion will be noted for the record.
20
With respect to all other participants, we
21 ask
in the interest of fairness that they address
22 any
current or previous financial involvement with
23 any
firm whose product they may wish to comment
24
upon.
25
Ted Treves is Chief of the Division of
11
1
Nuclear Medicine at Children's Hospital, Harvard,
2 who
was an invited speaker for today, will not be
3
able to attend.
4
DR. CHESNEY: Thank you. Our first
5
speaker this morning will be Dr. Rosemary Roberts,
6 who
is going to offer a welcome on behalf of the
7
Office of Counteterrorism and Pediatric Drug
8
Development.
9 Welcome
10
DR. ROBERTS: Good morning. I would like
11 to
take this opportunity to thank you all for
12
coming today. I would also like
to thank the
13
"Murphys" for allowing me to come up and speak. I
14
rarely get to do it; you know, I am sort of the guy
15 in
the middle. I know some of you had to
16
experience much worse weather than we have here
17
today in order to get here so we certainly
18
appreciate all of your dedication in coming.
19
Our office, as you know, has two high
20
priority areas, counterterrorism which we might be
21
dealing with today unfortunately, and also
22
pediatric drug development, and we are certainly
23
happy that we have this program today.
24
We are excited about learning more about
25
cardiac imaging and having this opportunity to
12
1
discuss it and have such a distinguished group of
2
people here to help us see how to move forward in
3
this area. So, thank you very
much for coming. I
4
hope that you have a good day and we appreciate all
5 the
advice that you can give us.
6
One other thing, as you know because Diane
7
Murphy mentioned it yesterday, with the recent
8
legislation, the Pediatric Research Equity Act, we
9 now
have a full pediatric advisory committee.
We
10 are
working on that charter and hope to have
11
something going on with that in the next couple of
12
months and then we will be setting up that advisory
13
committee. Thank you.
14
DR. CHESNEY: Thank you, Dr.
Roberts. Our
15
next speaker is Dr. Solomon Iyasu who is going to
16
bring us up to date on the adverse event reports as
17
required by the BPCA.
18
Adverse Event Reports per Section
17 of BPCA
19
DR. IYASU: Good morning. Yesterday I
20
presented adverse event reports for paroxetine and
21
citalopram pertaining to psychiatric adverse
22
events. Today I will be
presenting on adverse
23
events reported for paroxetine and citalopram and
24
then, subsequently, I will report on adverse events
25 for vinorelbine and pravastatin.