Twenty-seventh meeting of the biological response modifiers advisory committee



Download 0,63 Mb.
Page1/18
Date conversion19.05.2017
Size0,63 Mb.
  1   2   3   4   5   6   7   8   9   ...   18






FOOD AND DRUG ADMINISTRATION


CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

TWENTY-SEVENTH MEETING OF THE

BIOLOGICAL RESPONSE MODIFIERS ADVISORY COMMITTEE

8:40 a.m.


Thursday, July 13, 2000

Hilton Hotel

620 Perry Parkway

Gaithersburg, Maryland 20877


ATTENDEES
COMMITTEE MEMBERS:
DANIEL R. SALOMON, M.D., Chairman

Associate Professor

Department of Molecular and Experimental Medicine

The Scripps Research Institute

10550 N. Torrey Pines Road, MEM 55

La Jolla, California 92037


GAIL DAPOLITO, Executive Secretary

Scientific Advisors & Consultants Staff

Center for Biologics Evaluation and Research

Food and Drug Administration

1401 Rockville Pike

Rockville, Maryland 20852-1448


RICHARD E. CHAMPLIN, M.D.

Professor of Medicine

Department of Blood and Marrow Transplantation

University of Texas M.D. Anderson Cancer Center

1515 Holcombe Boulevard, Box 24

Houston, Texas 77030


JOANNE KURTZBERG, M.D.

Professor of Pediatrics

Department of Pediatrics

Duke University Medical Center

Box 3350, Suite 1400 North Pavilion

Durham, North Carolina 27710


W. MICHAEL O'FALLON, PH.D.

Professor of Biostatistics

Department of Health Sciences Research

Mayo Clinic

Harwick Building, Room 766-A

Rochester, Minnesota 55905


EDWARD A. SAUSVILLE, M.D., PH.D.

Associate Director

Developmental Therapeutics Program

National Cancer Institute

National Institutes of Health

6116 Executive Boulevard, Suite 500

Rockville, Maryland 20892
ATTENDEES (Continued)
COMMITTEE MEMBERS: (Continued)
ALICE WOLFSON, J.D.

Bourhis, Wolfson and Schlichtmann

1050 Battery Street

San Francisco, California 94111

TEMPORARY VOTING MEMBER:
HUGH AUCHINCLOSS, JR., M.D.

Professor of Surgery

Department of Surgery

Harvard Medical School

Massachusetts General Hospital

GRB504, 55 Fruit Street

Boston, Massachusetts 02144-2696

CONSULTANTS:


DAVID A. DRACHMAN, M.D.

Professor and Chair

Department of Neurology

University of Massachusetts Medical School

55 Lake Avenue N., Room S5-753

Worcester, Massachusetts 01655


THOMAS B. FREEMAN, M.D.

Professor

Department of Neurosurgery

University of South Florida College of Medicine

#4 Columbia Drive, Suite 730

Tampa, Florida 33606


STEVEN A. GOLDMAN, M.D., PH.D.

Professor of Neurology and Neuroscience

Department of Neurology and Neuroscience

Cornell University Medical College

1300 York Avenue

New York, New York 10021


ATTENDEES (Continued)
CONSULTANTS: (Continued)
JEFFREY H. KORDOWER, PH.D.

Professor of Neurological Sciences

Department of Neurological Sciences

Rush Presbyterian-St. Luke's Medical Center

2242 W. Harrison Street

Chicago, Illinois 60612


JOHN W. McDONALD, III, M.D., PH.D.

Assistant Professor of Neurology and

Neurological Surgery

Department of Neurology

Washington University School of Medicine

Campus Box 8111

660 South Euclid Avenue

St. Louis, Missouri 63110-1093


VASSILIS E. KOLIATSOS, M.D.

Associate Professor

Department of Pathology

The Johns Hopkins University School of Medicine

Ross 558 Research Building

720 Rutland Avenue

Baltimore, Maryland 21205-2196
JEFFREY D. MACKLIS, M.D.

Associate Professor of Neurology

Department of Neurology

Harvard Medical School

Children's Hospital

354 Enders Building

320 Longwood Avenue

Boston, Massachusetts 02115


MAHENDRA S. RAO, M.D., PH.D.

Associate Professor

Department of Neurobiology and Anatomy

University of Utah Medical School

531 Wintrobe Building

50 North Medical Drive

Salt Lake City, Utah 84132
ATTENDEES (Continued)
CONSULTANTS: (Continued)
EVAN Y. SNYDER, M.D., PH.D.

Assistant Professor in Neurology

Department of Pediatrics

Harvard Medical School

248 Enders Building

300 Longwood Avenue

Boston, Massachusetts 02115
JEREMY SUGARMAN, M.D., M.P.H., M.A.

Associate Professor of Medicine

Center for Study of Medical Ethics and Humanities

Duke University Medical Center

Box 3040, Trent Drive

Durham, North Carolina 27710


CATHERINE M. VERFAILLIE, M.D.

Professor of Medicine

Department of Medicine

University of Minnesota Medical Center

Cancer Center Research Building, Room 660F

Box 806 Mayo

420 Delaware Street, S.E.

Minneapolis, Minnesota 55455


MICHAEL D. WALKER, M.D.

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Neuroscience Center, Room 2223

6001 Executive Boulevard

Bethesda, Maryland 208892-2581

GUESTS:
FRED H. GAGE, PH.D.

Professor

Laboratory of Genetics

The Salk Institute

10010 N. Torrey Pines Road

La Jolla, California 92037


ATTENDEES (Continued)
GUESTS: (Continued)
JOHN D. GEARHART, PH.D.

Professor and Director of Developmental Genetics

Department of Obstetrics and Gynecology

The Johns Hopkins University School of Medicine

600 N. Wolfe Street, Park Building, B2-202

Baltimore, Maryland 21287-2501


RICHARD C. MULLIGAN, M.D.

Mallinckrodt Professor of Genetics

Department of Genetics

Harvard Medical School

Children's Hospital

861 Enders Building

320 Longwood Avenue

Boston, Massachusetts 02115


MARK NOBLE, PH.D.

Professor

Department of Oncological Sciences

Huntsman Cancer Institute

University of Utah

2000 Circle of Hope, Room 4280

Salt Lake City, Utah 84112
JOHN Q. TROJANOWSKI, M.D., PH.D.

Professor

Department of Pathology and Laboratory Medicine

University of Pennsylvania School of Medicine

3rd Floor Maloney Building

3600 Spruce Street

Philadelphia, Pennsylvania 19104-4283

NIH PARTICIPANT:


ARLENE CHIU, PH.D.

Project Director

National Institute of Neurological Disorders and Stroke

National Institutes of Health

6001 Executive Boulevard, Room 2205

Bethesda, Maryland 20892


ATTENDEES (Continued)
FOOD AND DRUG ADMINISTRATION PARTICIPANTS:
DONALD W. FINK, JR., PH.D.

Biologist

Division of Cellular and Gene Therapies

Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-527)

Rockville, Maryland 20852
MALCOLM MOOS, JR., M.D., PH.D.

Medical Officer

Division of Cellular and Gene Therapies

Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-524)

Rockville, Maryland 20852
PHILLIP D. NOGUCHI, M.D.

Director


Division of Cellular and Gene Therapies

Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-515)

Rockville, Maryland 20852
MERCEDES SERABIAN, M.S.

Division of Cellular and Gene Therapies

Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-579)

Rockville, Maryland 20852


JAY P. SIEGEL, M.D.

Director


Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-500)

Rockville, Maryland 20852


BARBARA WILCOX, PH.D

Biologist

Division of Therapeutic Proteins

Office of Therapeutics Research and Review

Center for Biologics Evaluation and Research

1401 Rockville Pike (HFM-524)

Rockville, Maryland 20852
ATTENDEES (Continued)
ALSO PRESENT:
AUSIM AZIZI, M.D., PH.D.

MCP Hahnemann University


L. TONY BECK, PH.D.

Tissue Engineering Sciences


JONATHAN DINSMORE, PH.D.

Diacrin
CURT FREED, M.D.

University of Colorado
DARWIN PROCKOP, M.D., PH.D.

MCP Hahnemann University


LOLA M. REID, PH.D.

Renaissance Cell Technologies


JORDANA SONTAG
C O N T E N T S
AGENDA ITEM PAGE
CONFLICT OF INTEREST STATEMENT

by Ms. Gail Dapolito 15


FDA INTRODUCTION

by Dr. Malcolm Moos 19


OVERVIEW: STEM CELL BIOLOGY

CURRENT KNOWLEDGE AND UNANSWERED QUESTIONS

by Dr. John Gearhart 24
ISOLATION, IDENTIFICATION, AND CHARACTERIZATION

OF BONE MARROW-DERIVED NON-HEMATOPOIETIC STEM

CELLS CAPABLE OF ASSUMING NEURONAL PHENOTYPES

by Dr. Catherine Verfaillie 61


CHARACTERIZATION OF LINEAGE-RESTRICTED,

SELF-RENEWING PRECURSORS FROM

NEUROEPITHELIAL STEM CELLS

by Dr. Mahendra Rao 101


ISOLATION, IDENTIFICATION, AND CHARACTERIZATION

OF ADULT HUMAN NEURAL PROGENITOR CELLS

by Dr. Steven Goldman 128
ANTICIPATING ETHICAL ISSUES IN CLINICAL EXPERIMENTS

USING STEM CELLS FOR NEUROLOGICAL DISORDERS

by Dr. Jeremy Sugarman 173
OVERVIEW: ANIMAL MODELS FOR PROGNOSTIC SAFETY

ASSESSMENT OF NEURAL STEM CELL TRANSPLANTATION

IN HUMANS

by Dr. Fred Gage 224


ANIMAL MODELS FOR EVALUATING CELL THERAPY OF

NEURODEGENERATIVE DISEASES

by Dr. John Trojanowski 258
MIGRATION AND INTEGRATION OF TRANSPLANTED STEM

CELLS WITHIN THE RECIPIENT NERVOUS SYSTEM

by Dr. Evan Snyder 298
ANIMAL MODELS OF SPINAL CORD INJURY AS

PARADIGMS FOR STEM CELL THERAPY

by Dr. John McDonald 326

P R O C E E D I N G S

(8:40 a.m.)

DR. SALOMON: Good morning, everybody. I'd like to welcome you to the latest meeting of the FDA's Biological Response Modifiers Advisory Committee. My name is Dan Salomon. I've got the pleasure of chairing this session today and tomorrow. Again, I'd like to welcome all of you to the Hilton Hotel.

What I always try and do at the beginning of these sessions just so that we get to know each other because a lot of people here don't know each other -- I certainly don't know everybody on the committee. There are some experts here from the field of neural stem cell transplantation and neural science that I'd like to have introduce themselves. So, what we've usually done is just gone around the table so everybody gets a quick idea of who's sitting here. So, I'd like to do that. It's a little more difficult in this setting because of the way we've sort of staggered these chairs. It's usually easier because it's a circle, but if we could start maybe at the last table in the back right and sort of go through there. Can you just tell us briefly who you are and your area of interest?

DR. CHIU: Arlene Chiu and I'm from NINDS, the Neurology Institute.

DR. MULLIGAN: I'm Rich Mulligan from Harvard Medical School and Children's Hospital and involved in stem cell research and gene transfer research.

DR. NOBLE: Mark Noble, University of Rochester. I'm a precursor cell biologist working in both general principles in precursor cell biology and in studying oligodendrocyte biology and repair of demyelinating damage.

DR. GEARHART: John Gearhart, Johns Hopkins Medicine, interested in human embryonic stem cells.

DR. GAGE: Fred Gage from the Salk Institute. I'm a neurobiologist.

DR. GOLDMAN: (Inaudible.)

DR. SALOMON: I should point out to everyone that you press the button. This little red light turns on for all us who forget to turn it back off again after you've spoken.

DR. RAO: Mehandra Rao from the University of Utah. I'm a neurobiologist interested in stem cells in the nervous system.

DR. SNYDER: Evan Snyder, Children's Hospital, Boston. I'm a neurobiologist and also a pediatrician, and I study stem cell biology.

DR. VERFAILLIE: Catherine Verfaillie at the University of Minnesota. I am a hematologist. I'm interested in stem cells from bone marrow.

DR. O'FALLON: Michael O'Fallon, Mayo Clinic, a member of the committee. I'm a biostatistician. I'm not quite sure what I'm going to make of all this basic science here in the next two days, but I'll be very interested.

(Laughter.)

MS. WOLFSON: Alice Wolfson. I'm an attorney from San Francisco and I'm the consumer representative.

MS. DAPOLITO: Gail Dapolito, Executive Secretary for the committee.

DR. SALOMON: Dan Salomon. I'm from the Scripps Research Institute in La Jolla, California. My interests are in gene therapy, hematopoietic stem cell transplantation, and islet cell transplantation and organ transplantation.

DR. SAUSVILLE: My name is Ed Sausville. I'm a medical oncologist from the National Cancer Institute in the Developmental Therapeutics Program, and my interest is in the development of novel small molecules and biologicals for the treatment of cancer.

DR. AUCHINCLOSS: My name is Hugh Auchincloss, and I'm a transplant surgeon at Harvard Medical School and a very recent member of the Biological Response Modifiers Committee.

DR. CHAMPLIN: Richard Champlin. I'm with the blood and marrow transplant program at the M.D. Anderson Cancer Center. I'm a hematologist.

DR. DRACHMAN: David Drachman, U Mass Medical Center. I'm a neurologist with an interest in Alzheimer's and other degenerative disorders.

DR. KOLIATSOS: Vassilis Koliatsos from Johns Hopkins. I'm a neurobiologist and clinician interested in neuroplasticity and the mechanisms of regeneration in CNS in the context of neurodegenerative disorders.

DR. KORDOWER: Jeff Kordower from Rush Presbyterian Medical Center in Chicago. I'm interested in gene therapy and cell transplantation.

DR. MACKLIS: Jeffrey Macklis from Children's Hospital and Harvard Medical School. My lab studies the repair of circuitry in the cerebral cortex by neural transplantation or activation of endogenous precursors.

DR. WALKER: Michael Walker, neurosurgeon, Neurology Institute, NIH.

DR. WILCOX: I'm Barbara Wilcox. I'm a neurobiologist with CBER.

MS. SERABIAN: I'm Mercedes Serabian with the Office of Therapeutics Research and Review of the Division of Clinical Trials. I'm a toxicology reviewer.

DR. FINK: I'm Donald Fink with the Division of Cell and Gene Therapy. I'm interested in neurotrophic factors.

DR. MOOS: Malcolm Moos, also from Cellular and Gene Therapy. My research interests are in pattern formation and cell and tissue fate specification.

DR. NOGUCHI: I'm Phil Noguchi, Director of Cell and Gene Therapy in the Office of Therapeutics.

DR. SIEGEL: Jay Siegel, Director of the Office of Therapeutics.

DR. SALOMON: Thank you all very much. Again, welcome.

I have some administrative things to quickly go over.

First, I'd like to welcome two new members of the Biological Response Modifiers Advisory Committee: Dr. Joanne Kurtzberg and Ms. Alice Wolfson, our new consumer representative.

There are also five panelists today who have been introduced but who are participating as guests, and I'd like to read their names just into the record. It's Dr. Fred Gage, Dr. John Gearhart, Dr. Richard Mulligan, Dr. Mark Noble, Dr. John Trojanowski, and Dr. Arlene Chiu.

I've also been asked to inform you that there are some revised questions in the blue folders. This continues to be an iterative process. Who knows. There may be revised questions tomorrow too.

What we're going to do is have presentations today with some discussion certainly. However, when discussions begin to veer toward things that are very specific questions for tomorrow, we'll kind of get into them a little bit and then decide to put them off or amplify them or return to them tomorrow. We'll just have to see what the chemistry is for that.

Finally, as Chair, I feel like the most important thing that happens in the next two days is that everybody sitting at the table today, as well as those of you in the public, feel like you have had access to make your points clear and add to the conversation. I think that's what we're here to do. Certainly on my part, there's no specific agenda except to address the questions, as best we can, that the FDA has put to us. So, if at any time, as things progress two days, somebody feels like I didn't get my point across or something, I really would rather have you come to me at that point and I will do everything possible to bring the point back around to discussion and have everything included. I say that also for the people in the audience.

So, with that, Gail Dapolito will read us the conflict of interest statement.

MS. DAPOLITO: Yes. Good morning, Dr. Salomon.

I'd like to also take this opportunity to introduce Ms. Rosanna Harvey, the committee management specialist. She and Ms. Denise Royster will be at the registration table to help out with any questions or assistance you might need for the committee.

I'd like to read the conflict of interest statement. This announcement is made part of the public record at this meeting of the Biological Response Modifiers Advisory Committee on July 13 and 14, 2000.

Pursuant to the authority granted under the committee charter, the Director of FDA's Center for Biologics Evaluation and Research has appointed Dr. Hugh Auchincloss as a temporary voting member.

Based on the agenda made available, it has been determined that the agenda addresses general matters only. For this meeting, general matters waivers have been approved by the agency for all special government employees who are participants. The general nature of the matters to be discussed by the committee will not have a unique and distinct effect on any of the participants' personal or imputed financial interests.

In regards to FDA's invited guests, the agency has determined that the services of these guests are essential. The following interests are being made public to allow meeting participants to objectively evaluate any presentation and/or comments made by the guests.

Dr. Arlene Chiu is employed by the National Institute of Neurological Disorders and Strokes, NIH. Dr. Fred Gage is employed by the Salk Institute. He is a scientific advisor for Cell Genysis, Signal Therapeutics, and Stem Cell, Inc. and has financial interests in several firms that could be affected by the committee discussions.

Dr. John Gearhart is employed by Johns Hopkins University. He receives financial support for his laboratory from Geron.

Dr. Richard Mulligan is employed by Harvard University.

Dr. Mark Noble is employed by the University of Utah. He's also a founding scientist of Acorda Therapeutics. He consults with Acorda and has a financial interest in a firm that could be affected by the committee discussions.

Dr. John Trojanowski is employed by the University of Pennsylvania School of Medicine. He's the co-founder of Layton BioScience, serves as the principal investigator on several federally supported grants, and has a financial interest in a firm that could be affected by the committee discussions.

In the event that the discussions involve other products or firms not already on the agenda for which FDA's participants have a financial interest, the participants are aware of the need to exclude themselves from such involvement and their exclusion will be noted for the public record.

With respect to all other meeting participants, we ask in the interest of fairness that you state your name, affiliation, and address any current or previous financial involvement with any firm whose product you wish to comment upon.

Copies of the waivers addressed in this announcement are available by written request under the Freedom of Information Act.

At this time we would also like to request that as a courtesy to the participants and to your neighbors in the audience that cellular phones be turned off. Please step outside in the foyer if you wish to use your cell phone. We also ask that pagers be set on the silent mode.

Thank you very much. Dr. Salomon, I'll turn it over to you.

DR. SALOMON: Basically the only other thing I'll say -- you guys got the drill as we went around. One of the things that's very important is that we create a written record. Just to make it easier for the transcriber, try and speak every time into the microphone, and when you're done speaking, turn the thing off, otherwise it picks up the background and she won't be able to get a clear recording.

Then let's start. We begin with the FDA introduction by Malcolm Moos.

DR. MOOS: Good morning, everyone. I'd like to make a few general remarks aimed largely at the audience because they're not quite as familiar with the process of these advisory committee meetings as some of those of us sitting around the table.

One of the more commonly held models of the nature of the interactions between the Food and Drug Administration and its constituent body as the public/patient advocacy groups and so forth is depicted schematically on the first slide.

Now, although I'd like to point out that if circumstances warrant, we do have the statutory authorities for things to degenerate to this level.

(Laughter.)

DR. MOOS: By and large, that's not how it works.

In fact, if we go back to civics 101, it's important to remember that the public, through the President and cabinet officials and through Congress, delegates to us the job of riding herd on the development of promising new therapies. In fact, one thing that we are empowered specifically to do, in order to help us do our jobs right, is to go directly to experts in the public in order to gain the expertise that we need to approach difficult, new issues.

Now, certainly the FDA has to be sensitive to emerging technologies. For those of you in the back who can't read the caption, it says, "Look what they're doing," they being the folks who've gotten the clue that flying is faster than walking.

So, it's natural for us to start looking for new technologies with enthusiasm, but at the same time, it's important to understand that -- the caption reads, "early experiments in transportation" -- there are certain pitfalls that can be anticipated. And perhaps more dangerous than difficulties that are obvious are cases that arise when we are confident in our abilities, we think that we are cruising at altitude and that everything is going to be a smooth flight, when in fact our judgments have blinded us to the obvious potential for great misfortune.

Although I think Mr. Larsen's cartoons make some of these points very elegantly, I don't want anyone to get the idea that we think of this as a big joke. There is great excitement in the issue of stem cell biology, but at the same time, there are various types of hazards, some of which we can foresee, some of which we can't. It is important to let everyone know that we have to be very sensitive to the fact that the most fundamental tenet of clinical medicine is: "First do no harm."

The task and advisory committee meeting I think is summed well by what a Hewlett Packard executive formulated as the quadrants of confidence. He started with conscious confidence. You know something and you know you know it. I think this quadrant right now is perhaps the smallest of the ones that we have. It will be very useful for us to establish as a group what sorts of things about the biology, the manufacture, the testing of stem cells we are fairly confident in that we think we know.

  1   2   3   4   5   6   7   8   9   ...   18


The database is protected by copyright ©sckool.org 2016
send message

    Main page