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OCR for page R1
CONSIDERATIONS FOR ENSURING SAFETY AND EFFICACY
OF VACCINES AND THERAPEUTIC PROTEINS
MANUFACTURED BY USING PLATFORM APPROACHES
SUMMARY OF A WORKSHOP
Jeffrey Fox, Marilee Shelton-Davenport, and India Hook-Barnard, Rapporteurs
Board on Life Sciences
Division on Earth and Life Studies
NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW, Washington, DC
20001
NOTICE: The project that is the subject of this report was approved by the Governing
Board of the National Research Council, whose members are drawn from the councils of
the National Academy of Sciences, the National Academy of Engineering, and the
Institute of Medicine. The members of the committee responsible for the report were
chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract W911NF-07-C-0081between the National
Academy of Sciences and Department of the Army. Any opinions, findings, conclusions,
or recommendations expressed in this publication are those of the authors and do not
necessarily reflect the views of the organizations or agencies that provided support for the
project.
International Standard Book Number - 13: 978-0-309-15321-8
International Standard Book Number - 10: 0-309-15321-2
Additional copies of this report are available from:
The National Academies Press
500 Fifth Street, NW
Lockbox 285
Washington, DC 20055
(800) 624-6242 or
(202) 334-3313 (in the Washington metropolitan area)
http://www.nap.edu
Copyright 2010 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished
scholars engaged in scientific and engineering research, dedicated to the furtherance of science and
technology and to their use for the general welfare. Upon the authority of the charter granted to it by the
Congress in 1863, the Academy has a mandate that requires it to advise the federal government on
scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National
Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its
administration and in the selection of its members, sharing with the National Academy of Sciences the
responsibility for advising the federal government. The National Academy of Engineering also sponsors
engineering programs aimed at meeting national needs, encourages education and research, and recognizes
the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of
Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the
services of eminent members of appropriate professions in the examination of policy matters pertaining to
the health of the public. The Institute acts under the responsibility given to the National Academy of
Sciences by its congressional charter to be an adviser to the federal government and, upon its own
initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of
the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate
the broad community of science and technology with the Academy’s purposes of furthering knowledge and
advising the federal government. Functioning in accordance with general policies determined by the
Academy, the Council has become the principal operating agency of both the National Academy of
Sciences and the National Academy of Engineering in providing services to the government, the public,
and the scientific and engineering communities. The Council is administered jointly by both Academies
and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair,
respectively, of the National Research Council.
www.national-academies.org
iii
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NATIONAL RESEARCH COUNCIL STANDING COMMITTEE ON
BIODEFENSE AT THE US DEPARTMENT OF DEFENSE
JENNIE HUNTER-CEVERA (Chair), RTI International, Research Triangle Park, NC
L. GARRY ADAMS, Texas A&M University, College Station, TX
JOHN F. ALDERETE, Washington State University, Pullman, WA
EDWARD J. ARCURI, Novartis Vaccines and Diagnostics, Inc., Cambridge, MA
MICHAEL ASCHER, University of California, Davis, CA
LESLIE BENET, University of California, San Francisco, CA
PHILIP E. COYLE III, Science Strategies, Sacramento, CA
STEPHEN W. DREW, Drew Solutions and Science Partners, LLC, Summit, NJ
DENISE FAUSTMAN, Harvard Medical School, Massachusetts General Hospital,
Charlestown, MA
HARRY GREENBERG, Stanford University, Stanford, CA
CHARLES HOBBS, Lovelace Respiratory Research Institute, Albuquerque, NM
THOMAS INGLESBY, University of Pittsburgh Medical Center, Baltimore, MD
JAMES A. MARKS, University of California, San Francisco, CA
TIMOTHY MOSHIER, Syracuse Research Corporation, North Syracuse, NY
FRED MURPHY, University of Texas Medical Branch, Galveston, TX
KAREN NELSON, J. Craig Venter Institute, Rockville, MD
PETER A. PATRIARCA, Biologics Consulting Group, Inc., Bethesda, MD
JOHN A. SMITH, University of Alabama, Birmingham, AL
JIM SWEARENGEN, National Biodefense Analysis and Countermeasures Center,
Frederick, MD
GRIFFIN TROTTER, Saint Louis University Center for Health Care Ethics, St. Louis,
MO
DAVID H. WALKER, University of Texas Medical Branch, Galveston, TX
Staff
MARILEE K. SHELTON-DAVENPORT, Study Director
INDIA HOOK-BARNARD, Program Officer
REBECCA L. WALTER, Senior Program Assistant
NORMAN GROSSBLATT, Senior Editor
AMANDA L. MAZZAWI, Program Assistant
Sponsor
DEPARTMENT OF DEFENSE TRANSFORMATIONAL MEDICAL
TECHNOLOGIES INITIATIVE
iv
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PLANNING GROUP FOR THE WORKSHOP ON CONSIDERATIONS FOR
ENSURING SAFETY AND EFFICACY OF VACCINES AND THERAPEUTIC
PROTEINS MANUFACTURED BY USING PLATFORM APPROACHES
JENNIE HUNTER-CEVERA (Chair), RTI International, Research Triangle Park, NC
EDWARD J. ARCURI, Novartis Vaccines and Diagnostics, Inc., Cambridge, MA
STEPHEN W. DREW, Drew Solutions and Science Partners, LLC, Summit, NJ
PETER A. PATRIARCA, Biologics Consulting Group, Inc., Bethesda, MD
Staff
MARILEE K. SHELTON-DAVENPORT, Study Director
INDIA HOOK-BARNARD, Program Officer
REBECCA L. WALTER, Senior Program Assistant
v
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BOARD ON LIFE SCIENCES
Members
KEITH R. YAMAMOTO (Chair), University of California, San Francisco, CA
ANN M. ARVIN, Stanford University School of Medicine, Stanford, CA
BONNIE L. BASSLER, Princeton University, Princeton, NJ
VICKI L. CHANDLER, Gordon and Betty Moore Foundation, Palo Alto, CA
SEAN EDDY, HHMI Janelia Farm Research Campus, Ashburn, VA
MARK D. FITZSIMMONS, John D. and Catherine T. MacArthur Foundation, Chicago,
IL
DAVID R. FRANZ, Midwest Research Institute, Frederick, MD
LOUIS J. GROSS, University of Tennessee, Knoxville, TN
JO HANDELSMAN, Yale University, New Haven, CT
CATO T. LAURENCIN, University of Connecticut Health Center, Farmington, CT
JONATHAN D. MORENO, University of Pennsylvania, Philadelphia, PA
ROBERT M. NEREM, Georgia Institute of Technology, Atlanta, GA
CAMILLE PARMESAN, University of Texas, Austin, TX
MURIEL E. POSTON, Skidmore College, Saratoga Springs, NY
ALLISON G. POWER, Cornell University, Ithaca, NY
BRUCE W. STILLMAN, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
CYNTHIA WOLBERGER, Johns Hopkins University School of Medicine, Baltimore,
MD
MARY WOOLLEY, Research!America, Alexandria, VA
Staff
FRANCES E. SHARPLES, Director
JO L. HUSBANDS, Scholar/Senior Project Director
ADAM P. FAGEN, Senior Program Officer
MARILEE K. SHELTON-DAVENPORT, Senior Program Officer
INDIA HOOK-BARNARD, Program Officer
ANNA FARRAR, Financial Associate
CARL-GUSTAV ANDERSON, Senior Program Assistant
AMANDA P. CLINE, Senior Program Assistant
REBECCA L. WALTER, Senior Program Assistant
AMANDA L. MAZZAWI, Program Assistant
vi
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PREFACE
The US Department of Defense (DOD) is developing new efforts to protect
warfighters from disease and biologic-warfare agents. The DOD Transformational
Medical Technologies Initiative (TMTI) seeks to shorten the timeline for development of
medical measures to counter emerging biologic-warfare threats: genetically engineered
and other nontraditional toxins, virulence factors, and microorganisms. One goal of the
TMTI is development of platforms for identifying unknown agents and developing
countermeasures so that within five years an infrastructure will be in place for reacting
quickly to a variety of threats, including agents that have been genetically engineered.
In response to a request from the Office of the Secretary of Defense, the National
Academies formed the Standing Committee on Biodefense at the US Department of
Defense. One purpose of the standing committee is to convene periodic meetings to
discuss potential avenues for research, development, demonstration, and practical
operational implementation of DOD's biologic-defense programs. Another purpose is to
develop and coordinate studies and other activities in this field at the National
Academies. On September 15, 2008, the National Academies held the workshop
“Considerations for Ensuring Safety and Efficacy of Vaccines and Therapeutic Proteins
Manufactured by Using Platform Approaches”. The workshop was planned and
organized by an ad hoc planning committee made up of members of the standing
committee. The charge to the planning committee (see Appendix A) was to bring together
scientists from academe, government, and the biotechnology industry to identify and
discuss challenges and ideas related to the TMTI’s vision of developing countermeasures
within a few months after an agent is identified. The workshop focused (see Appendix B
for agenda) on manufacturing processes and specifically on the development of
"manufacturing platforms"— repeatable components of manufacturing that reduce both
development time and risk. An underlying assumption was that demonstrating that
integrated platforms can reliably produce safe and efficacious countermeasures might
shorten the regulatory approval process.
Participants discussed manufacturing-related characteristics of monoclonal
antibodies and vaccines. Although the planning committee understood that the TMTI
efforts are broader than biologics and that TMTI platform approaches for biologics
extend beyond monoclonal antibodies and vaccines, the planning committee believed that
focusing on monoclonal antibodies and vaccines could illustrate some of the promise and
challenges of platform approaches.
This summary is based on a transcript of the workshop, and statements are
attributed to specific participants according to the transcript. It is presented as a narrative
rather than a strict chronology to highlight the major themes that emerged from the
meeting. Views expressed in the summary are those of the individual participants and are
not necessarily those of the planning committee, the National Academies, or the project
sponsor.
Jennie Hunter-Cevera, Chair
Planning Group for the Workshop on Considerations for Ensuring Safety and Efficacy of
Vaccines and Therapeutic Proteins Manufactured by Using Platform Approaches
vii
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ACKNOWLEDGMENTS
The committee thanks those who made this workshop possible through their
participation—speakers and panelists (their names and biographies are available in
Appendix C) and the other workshop attendees. The workshop was successful in large
part owing to the advance work conducted by the workshop planning group: Jennie
Hunter-Cevera, Edward J. Arcuri, Stephen W. Drew, and Peter A. Patriarca. In
accordance with National Research Council policies, the workshop planners were not
involved in the preparation of this summary. James A. Marks, a member of the standing
committee, provided insightful comments on early drafts of the summary.
This report has been reviewed in draft form by individuals chosen for their
diverse perspectives and technical expertise, in accordance with procedures approved by
the National Research Council’s Report Review Committee. The purpose of this
independent review is to provide candid and critical comments that will assist the
institution in making its published workshop summary as sound as possible and to ensure
that it meets institutional standards of objectivity, evidence, and responsiveness to the
charge. The review comments and the draft manuscript remain confidential to protect the
integrity of the deliberative process. We wish to thank the following individuals for their
review of this summary:
L. Garry Adams, Texas A&M University
Jonathan Coffman, Wyeth BioPharma
Peter A. Patriarca, Biologics Consulting Group, Inc.
Although the reviewers and Dr. Marks have provided many constructive
comments and suggestions, they were not asked to endorse the content nor did they see a
final draft of the summary before its release. The review of this summary was overseen
by P. Frederick Sparling, University of North Carolina. Appointed by the National
Research Council, he was responsible for making certain that an independent
examination of this summary was carried out in accordance with institutional procedures
and that all review comments were carefully considered. Responsibility for the final
content of this summary rests entirely with the institution.
ix
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CONTENTS
INTRODUCTION 1
TMTI Case for Versatile Production Platforms, 2
Discussion of TMTI Efforts, 3
PLATFORMS FOR LARGE-SCALE MONOCLONAL ANTIBODY
PRODUCTION 4
Presentation by Brian Kelley, 4
Presentation by Dane Zabriskie, 6
Discussion, 8
Suitability of Platforms and Supply Needed
Reducing Timeline
Manufacturing Production Capacity
Regulatory Issues
PLATFORMS FOR VACCINE PRODUCTION 11
Presentation by David Robinson, 11
Discussion, 12
Various Platforms
Manufacturing Facilities
Regulatory Issues
SUMMARY OF KEY POINTS 15
APPENDIXES 16
A. Statement of Task, 16
B. Agenda, 17
C. Biographies, 19
xi
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