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Committee on Accelerating the Research, Development, and Acquisition of
Medical Countermeasures Against Biological Warfare Agents
Medical Follow-up Agency
and
Board on Life Sciences
Lois M. Joellenbeck, Jane S. Durch, and Leslie Z. Benet, Editors
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. 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 Na-
tional Academy of Sciences, the National Academy of Engineering, and the Institute of Medi-
cine. The members of the committee responsible for the report were chosen for their special
competences and with regard for appropriate balance.
Support for this project was provided by Contract No. DAMD17-02-C-0099 between the
National Academy of Sciences and the U.S. Army. The views presented in this report are
those of the Institute of Medicine and National Research Council Committee on Accelerat-
ing the Research, Development, and Acquisition of Medical Countermeasures Against Bio-
logical Warfare Agents and are not necessarily those of the funding agencies.
Library of Congress Cataloging-in-Publication Data
Giving full measure to countermeasures : addressing problems in the DOD program to de-
velop medical countermeasures against biological warfare agents / Committee on Acceler-
ating the Research, Development, and Acquisition of Medical Countermeasures against Bio-
logical Warfare Agents, Medical Follow-up Agency and Board on Life Sciences ; Lois M.
Joellenbeck, Jane S. Durch, and Leslie Z. Benet, editors.
p. ; cm.
Includes bibliographical references.
ISBN 0-309-09153-5 (pbk.)
1. Biological warfare--Health aspects--United States. 2. Biological warfare--United
States--Safety measures. 3. Biological weapons--Health aspects--United States. 4. Biologi-
cal weapons--United States--Safety measures. 5. Medicine, Preventive--United States. 6.
Antitoxins--United States. 7. Vaccines--United States.
[DNLM: 1. United States. Dept. of Defense. 2. Biological Warfare--prevention &
control. 3. Drug Approval. 4. Antitoxins. 5. Military Personnel. 6. United States Govern-
ment Agencies. 7. Vaccines. ] I. Joellenbeck, Lois M. (Lois Mary), 1963- II. Durch, Jane. III.
Benet, Leslie Z. IV. Committee on Accelerating the Research, Development, and Acquisition
of Medical Countermeasures against Biological Warfare Agents.
UG447.8.G58 2004
358'.38--dc22
2004005890
Additional copies of this report are available from the National Academies Press, 500 Fifth
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Copyright 2004 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
Cover credit: The upper cover photograph is from a U.S. Department of Defense news pho-
tograph. [Online]. Available: http://www.defenselink.mil/photos/May1997/970422-F-
7719S-002.html.
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The National Academy of Sciences is a private, nonprofit, self-perpetuating soci-
ety of distinguished scholars engaged in scientific and engineering research, dedi-
cated 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. Bruce M. Alberts is president of the National
Academy of Sciences.
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The National Research Council was organized by the National Academy of Sci-
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Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair,
respectively, of the National Research Council.
www.national-academies.org
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COMMITTEE ON ACCELERATING THE RESEARCH,
DEVELOPMENT, AND ACQUISITION OF MEDICAL
COUNTERMEASURES AGAINST
BIOLOGICAL WARFARE AGENTS
LESLIE Z. BENET (Chair), Professor, Department of Biopharmaceutical
Sciences, School of Pharmacy, University of California, San
Francisco
WALTER E. BRANDT, Senior Program Officer, Malaria Vaccine
Initiative, Program for Appropriate Technology in Health
BARRY S. COLLER, Vice President for Medical Affairs, David
Rockefeller Professor of Medicine, and Head of the Laboratory of
Blood and Vascular Biology, The Rockefeller University
GLENNA M. CROOKS, President, Strategic Health Policy
International, Inc.
R. GORDON DOUGLAS, JR., Scientific Consultant
JACQUES S. GANSLER, Professor and Roger C. Lipitz Chair, Center
for Public Policy and Private Enterprise, School of Public Affairs,
University of Maryland
ANTHONY L. ITTEILAG, Independent Consultant
DENNIS L. KASPER, Executive Dean for Academic Programs, William
Ellery Channing Professor of Medicine, and Professor of
Microbiology and Molecular Genetics, Harvard Medical School
STEVEN J. KELMAN, Albert J. Weatherhead III and Richard W.
Weatherhead Professor of Public Management, John F. Kennedy
School of Government, Harvard University
RICHARD F. KINGHAM, Partner, Covington and Burling
PETER M. PALESE, Professor and Chair, Department of Microbiology,
Mount Sinai School of Medicine
PAUL D. PARKMAN, President, Parkman Associates
RONALD J. SALDARINI, Scientific Consultant
JANE E. SISK, Professor, Department of Health Policy, Mount Sinai
School of Medicine
ELAINE I. TUOMANEN, Professor and Chair, Department of
Infectious Diseases, St. Jude Children's Research Hospital
BENJAMIN J. WEIGLER, Director, Animal Health Resources, Division
of Shared Resources, Fred Hutchinson Cancer Research Center
JANET WESTPHELING, Associate Professor, Department of Genetics,
University of Georgia
v
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Medical Follow-up Agency Board Liaison
TIMOTHY R. GERRITY, Director, Bioengineering Institute, Worcester
Polytechnic Institute
Consultant
JAMES D. MARKS, Professor, Anesthesia and Pharmaceutical
Chemistry, University of California, San Francisco
Project Staff
LOIS JOELLENBECK, Senior Program Officer, Medical Follow-up
Agency
JANE DURCH, Senior Program Officer, Medical Follow-up Agency
KAREN KAZMERZAK, Research Associate, Medical Follow-up
Agency (through July 2003)
PHILLIP BAILEY, Senior Project Assistant, Medical Follow-up Agency
Auxiliary Staff
RICHARD N. MILLER, Director, Medical Follow-up Agency (to
November 2003)
RICK ERDTMANN, Director, Medical Follow-up Agency (since
November 2003)
JENNIFER KUZMA, Senior Program Officer, Board on Life Sciences,
Division on Earth and Life Studies (until January 2003)
FRANCES SHARPLES, Director, Board on Life Sciences, Division on
Earth and Life Studies
REINE HOMAWOO, Senior Project Assistant, Medical Follow-up
Agency
PAMELA RAMEY-MCCRAY, Administrative Assistant, Medical
Follow-up Agency
ANDREA COHEN, Financial Associate, Institute of Medicine
vi
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Reviewers
T his 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 Re-
view Committee. The purpose of this independent review is to provide
candid and critical comments that will assist the institution in making its
published report as sound as possible and to ensure that the report meets
institutional standards for objectivity, evidence, and responsiveness to the
study charge. The review comments and draft manuscript remain confi-
dential to protect the integrity of the deliberative process. We wish to
thank the following individuals for their review of this report:
JAMES L. BLANCHARD, Tulane Regional Primate Center
WILLIAM H. HABIG, Centocor, Inc.
ROBERT HELMS, The American Enterprise Institute
BRUCE KUHLIK, Pharmaceutical Research and Manufacturers of
America
MYRON M. LEVINE, University of Maryland at Baltimore
JOHN S. PARKER, Science Applications International Corporation
HOWARD R. SIX, Aventis Pasteur (retired)
FRED THOMPSON, Willamette University
JOHN P. WHITE, Harvard University
GEORGE WHITESIDES, Harvard University
Although the reviewers listed above have provided many construc-
tive comments and suggestions, they were not asked to endorse the con-
vii
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viii REVIEWERS
clusions or recommendations nor did they see the final draft of the report
before its release. The review of this report was overseen by Alexander
Flax, consultant, and Morton Swartz, Massachusetts General Hospital.
Appointed by the National Research Council and the Institute of Medi-
cine, they were responsible for making certain that an independent ex-
amination of this report was carried out in accordance with institutional
procedures and that all review comments were carefully considered. Re-
sponsibility for the final content of this report rests entirely with the
authoring committee and the institution.
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Preface
T he Gulf War of 19901991 renewed Cold War concerns that U.S. ser-
vice members might be exposed to chemical or biological warfare
agents on the battlefield. These concerns were reinforced after the
war upon discovery of Iraqi stockpiles of weaponized biological and
chemical agents.1 In 2001, the distribution of Bacillus anthracis spores
through the U.S. postal system renewed public awareness of the threats
posed by biological agents.
At the time of the Gulf War, only one medical countermeasure ap-
proved by the Food and Drug Administration (FDA)--the vaccine against
anthrax--was available to the Department of Defense (DoD) to protect
troops against possible biological warfare agents. In 2003, despite con-
gressional attention and good-faith efforts on the part of DoD scientists,
no new vaccines against biowarfare agents are available to service mem-
bers.2
In the National Defense Authorization Act for Fiscal Year 2002 (P.L.
107-107), Congress directed the Secretary of Defense to accelerate the
1United Nations Special Commission. 1999. UNSCOM: Chronology of Main Events. New
York: United Nations. [Online]. Available: http://www.un.org/Depts/unscom/Chronol-
ogy/chronologyframe.htm.
2Since 2000, the FDA has renewed the product license for existing supplies of smallpox
vaccine and has approved labeling ciprofloxacin (Cipro), tetracyclines (including doxycy-
cline), and penicillins for treatment of anthrax.
ix
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x PREFACE
department's efforts to develop FDA-licensed medical countermeasures
against biological warfare agents. In addition, the Secretary was directed
to contract with the Institute of Medicine (IOM) and the National Research
Council (NRC) for a study of the review and approval process for new
medical countermeasures in order to identify new approaches to acceler-
ate that process and to identify methods for ensuring that new counter-
measures will be safe and effective. To carry out the study, IOM and NRC
convened the Committee on Accelerating the Research, Development, and
Acquisition of Medical Countermeasures Against Biological Warfare
Agents.
The members of the committee bring to the study expertise in drug
and vaccine acquisition in DoD; vaccine and drug research, development,
testing, and evaluation in academia and the pharmaceutical and biotech-
nology industries; laboratory animal science; federal drug and vaccine
regulatory policy; legal and economic issues in drug and vaccine devel-
opment; and management processes in government and industry.
The committee has the following charge:
The committee will examine DoD's biowarfare countermeasure drug and
vaccine acquisition process. The acquisition process includes the early
science and technology development (research and development pro-
gram elements 6.1, 6.2, 6.3) and advanced development (program ele-
ments 6.4, 6.5) through the approval and licensure of products. The study
will not examine production and procurement processes. The committee
will identify factors that are impeding or slowing the acquisition pro-
cesses and will recommend strategies or options for accelerating these
processes.
Guided by discussion with DoD representatives and congressional
staff at its first meeting, the committee interpreted this charge as calling
for its work to focus on the manner in which DoD organizes and manages
research, development, and acquisition of medical countermeasures,
rather than on the details of specific scientific approaches. The medical
products covered by the study include vaccines, antitoxins, chemopro-
phylactics, and chemotherapeutics. In keeping with its charge, the com-
mittee did not examine the acquisition of diagnostic products or other
biodefense products, such as protective suits, decontamination equip-
ment, or sensors for detection of biological agents, that are also being de-
veloped as essential components of DoD's Chemical and Biological De-
fense Program. The military services and combatant commands have an
important role in these broader aspects of biodefense that were not a fo-
cus of this study.
Previous independent advisory committees requested by DoD re-
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PREFACE xi
leased reports in 2000 and 20023 addressing aspects of the development
and production of vaccines for military needs and providing important
context for the present study. Because those and other reports have dealt
in detail with some of the topics covered here, the committee chose in this
report to focus attention on the opportunities it identified for improve-
ment, rather than on extensive historical and background information. To
that end, the report begins with the committee's major recommendations
in Chapters 1 and 2, with additional, second-order recommendations in
Chapter 3. Brief background material on the current DoD program to de-
velop medical biowarfare countermeasures and the current status of
biowarfare countermeasures is provided in Appendix A.
The committee met six times between December 2002 and July 2003.
At five of those meetings, the committee met in public session for presen-
tations from and discussions with invited speakers (see Appendix B for
the agendas of the public sessions). Small subgroups of committee mem-
bers also participated in a series of informal meetings with officials from
the several DoD organizations with a role in the current Chemical and
Biological Defense Program (see Figure 2-1 for an organizational chart),
with congressional staff, and with representatives from DynPort Vaccine
Company, the National Institute of Allergy and Infectious Diseases
(NIAID) of the National Institutes of Health, the FDA, and the Depart-
ment of Homeland Security.
An interim report was submitted to the sponsor in March 2003.
As chair, I am very grateful to my fellow committee members for the
dedication and industry that they exhibited in addressing a very complex
and difficult problem. They willingly and enthusiastically participated in
the six formal meetings of the committee, and many were available for the
20 informal meetings with various governmental and other relevant con-
tacts as described above. Finally, the entire committee participated in four
conference calls as this report evolved. The committee was frequently pre-
sented with very contradictory opinions and recommendations, while the
landscape continually changed as the administration's response to per-
ceived bioterrorism threats and the progress of the war in Iraq brought
different perspectives to our charge.
3 Institute of Medicine. 2002. Protecting Our Forces: Improving Vaccine Acquisition and Avail-
ability in the U.S. Military. Lemon SM, Thaul S, Fisseha S, O'Maonaigh HC, eds. Washington,
DC: National Academies Press. Top FH Jr., Dingerdissen JJ, Habig WH, Quinnan GV Jr.,
Wells RL. 2000. DoD Acquisition of Vaccine Production: Report to the Deputy Secretary of
Defense by the Independent Panel of Experts. In DoD. 2001. Report on Biological Warfare
Defense Vaccine Research and Development Programs. Washington, DC: Department of Defense.
[Online]. Available: http://www.acq.osd.mil/cp/bwdvrdp-july01.pdf.
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xii PREFACE
The committee is also in debt to numerous officials from DoD, con-
gressional staff, senior leadership staff from DynPort Vaccine Company,
NIAID, FDA, and the Department of Homeland Security who assisted the
committee in its fact finding, and in particular our study contact with
DoD, Dr. Carol Linden. These individuals, as noted in Appendix C, gra-
ciously appeared before the committee at our formal meetings, sometimes
two or three times, to make presentations. In addition many of them often
attended the committee meetings when they were not making a formal
presentation, and they were always willing to be available to meet infor-
mally with subsets of the committee and to respond to questions from the
staff. We could not have completed our work in a timely manner without
the cooperation of these officials.
The committee and I are extremely grateful to the outstanding IOM
staff that tirelessly and with unselfish dedication helped to prepare this
report in a timely manner. We are particularly appreciative of our two
Senior Program Officers Lois Joellenbeck and Jane Durch, and the com-
mittee certifies that they are jewels, whose brilliance and worth shone
brightly in enlightening and assisting committee members in evaluating
the many controversial and technical issues related to the study. The com-
mittee also acknowledges and appreciated the work of Research Associ-
ate Karen Kazmerzak, and Senior Project Assistants Phillip Bailey and
Reine Homawoo, who were unflagging in their effective responses to com-
mittee needs. This level of commendation speaks well of Richard N.
Miller, the director of the Medical Follow-up Agency, who has assembled
such a responsive staff, and the committee thanks him for his support and
frequent inobtrusive input into its deliberations. We are grateful as well
to Bronwyn Schrecker, Clyde Behney, Janice Mehler, Jennifer Bitticks, Jen-
nifer Otten, and Andrea Cohen, the IOM and NRC staff who participated
in the report review, preproduction, dissemination, and financial man-
agement for the report.
Leslie Z. Benet, Ph.D.
Chair
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Contents
ABBREVIATIONS AND ACRONYMS xvii
EXECUTIVE SUMMARY 1
1 ENDING HALF-MEASURES FOR COUNTERMEASURES:
THE CHALLENGE AND MAJOR RECOMMENDATIONS 19
The Current Context for the Development of
Medical Countermeasures, 20
Problems Hindering the DoD Effort, 25
Are Medical Countermeasures a Priority?, 31
Recommendations for Change, 35
References, 40
2 ORGANIZING RESEARCH AND DEVELOPMENT FOR
MEDICAL COUNTERMEASURES TO ACCOMPLISH
ESSENTIAL FUNCTIONS 44
A DoD Agency for Acquisition of Medical Countermeasures
for Biological Defense, 45
Consideration of Alternative Approaches, 64
References, 71
xiii
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xiv CONTENTS
3 CHALLENGES IN THE RESEARCH AND DEVELOPMENT
OF MEDICAL COUNTERMEASURES AGAINST
BIOLOGICAL WARFARE AGENTS 73
Engaging Academia and Industry, 74
Supporting the Regulatory Process, 82
Overcoming Current and Potential Resource Bottlenecks, 89
Ensuring the Availability of a Well-Trained Workforce, 94
References, 97
APPENDIXES
A Background: The Current DoD Medical Biowarfare
Countermeasures Program 103
B Agendas for Information-Gathering Meetings 117
C Acknowledgments 127
D Biographical Sketches 131
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Figures, Tables, and Boxes
FIGURES
1-1 Budget authority for the medical biodefense component of the
Chemical and Biological Defense Program and other selected DoD
research, development, testing, and evaluation programs, FY 1996
2004, 34
2-1 Simplified representation of current offices and organizations with a
role in the DoD research, development, and acquisition program for
medical biological defense, 46
2-2 Placement of the proposed Medical Biodefense Agency within
DoD, 52
TABLES
1-1 Budget Authority for the Medical Biodefense Component of the
Chemical and Biological Defense Program (CBDP) and Other Se-
lected DoD Research, Development, Testing, and Evaluation Pro-
grams, FY 19962004, 32
2-1 Advantages and Disadvantages of Alternative Approaches to the Or-
ganization and Management of Research and Development of Medi-
cal Biodefense Countermeasures to Meet DoD Needs, 66
xv
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xvi FIGURES, TABLES, AND BOXES
A-1 Medical Countermeasures Available Against Biological Threat
Agents, 110
A-2 DoD-Related Research and Development Activities for Medical Bio-
logical Warfare Countermeasures, 112
BOXES
ES-1 Recommendations, 13
1-1 Events Related to the Development of Medical Biodefense Counter-
measures, 22
1-2 Factors in the Pace of Countermeasure Development and
Licensure, 26
2-1 Essential Functions of the DoD Research and Development
Program for Medical Countermeasures Against Biological Warfare
Agents, 48
2-2 Intramural Expertise Needed for a DoD Research and Development
Program for Vaccines and Other Medical Countermeasures, 51
3-1 Mechanisms for Engaging Academic Institutions, Industry, and Oth-
ers in the Private Sector in Federally Funded Research and Develop-
ment, 76
A-1 Key Features of DoD Policy and Requirements Concerning Acquisi-
tion and Use of Medical Countermeasures to Protect the Health of
Military Forces Against Biological Warfare Threat Agents, 106
A-2 Potential Biological Threats as Presented by DoD Medical Biological
Defense Research and Development Program, 108
A-3 Diseases and Biological Agents Identified by the CDC as Posing a
Threat to National Security, 109
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Abbreviations and Acronyms
AAE Army Acquisition Executive (Secretary of the Army)
ASD(HA) Assistant Secretary of Defense for Health Affairs
ATSD(NCB) Assistant to the Secretary of Defense for Nuclear and
Chemical and Biological Defense Programs
BoT botulinum toxoid vaccine
BSL biosafety level
CBD Chemical and Biological Defense Directorate
CBDP Chemical and Biological Defense Program
CBMS Chemical Biological Medical Systems
CDC Centers for Disease Control and Prevention
C.F.R. Code of Federal Regulations
cGMP current Good Manufacturing Practice
CJCS Chairman of the Joint Chiefs of Staff
CRADA Cooperative Research and Development Agreement
DARPA Defense Advanced Research Projects Agency
DATSD(CBD) Deputy Assistant to the Secretary of Defense for
Chemical and Biological Defense
DHHS Department of Health and Human Services
DHS Department of Homeland Security
DoD Department of Defense
DTRA Defense Threat Reduction Agency
DUS&T Dual-Use Science and Technology
xvii
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xviii ABBREVIATIONS AND ACRONYMS
DVC DynPort Vaccine Company
FDA Food and Drug Administration
FY fiscal year
GAO General Accounting Office
GMP Good Manufacturing Practice
IND Investigational New Drug
IOM Institute of Medicine
JPEO Joint Program Executive Office
JPEO-CBD Joint Program Executive Office for Chemical and
Biological Defense
JRO Joint Requirements Office
JRO-CBRN Joint Requirements Office for Chemical, Biological,
Radiological, and Nuclear Defense
JVAP Joint Vaccine Acquisition Program
MBDRP Medical Biological Defense Research Program
MCBDRP Medical Chemical and Biological Defense Research
Program
MCDRP Medical Chemical Defense Research Program
MIDRP Military Infectious Diseases Research Program
MITS Medical Identification and Treatment Systems
MRMC Medical Research and Materiel Command
NDA New Drug Application
NIAID National Institute of Allergy and Infectious Diseases
NIH National Institutes of Health
NRC National Research Council
OTA Office of Technology Assessment
PDUFA Prescription Drug User Fee Act
P.L. Public Law
SAFETY Act Support of Anti-terrorism by Fostering Effective
Technologies Act of 2002
SBIR Small Business Innovation Research
SECDEF Secretary of Defense
STTR Small Business Technology Transfer
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ABBREVIATIONS AND ACRONYMS xix
USAMMDA U.S. Army Medical Materiel Development Activity
USAMRIID U.S. Army Medical Research Institute of Infectious
Diseases
USAMRMC U.S. Army Medical Research and Materiel Command
U.S.C. United States Code
USD Under Secretary of Defense
USD(AT&L) Under Secretary of Defense for Acquisition, Technology,
and Logistics
USD(P&R) Under Secretary of Defense for Personnel and Readiness
WRAIR Walter Reed Army Institute of Research
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