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                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.