PROTECTING OUR FORCES
Improving Vaccine Acquisition and Availability in the U.S. Military
Stanley M. Lemon, Susan Thaul, Salem Fisseha, and Heather C. O’Maonaigh, Editors
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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.
Support for this project was provided by U.S. Army Medical Research and Materiel Command (Contract No. DAMD17-00-C-0003). The views presented in this report are those of the Institute of Medicine Committee on a Strategy for Minimizing the Impact of Naturally Occurring Infectious Diseases of Military Importance: Vaccine Issues in the U.S. Military and are not necessarily those of the funding agency.
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COMMITTEE ON A STRATEGY FOR MINIMIZING THE IMPACT OF NATURALLY OCCURRING INFECTIOUS DISEASES OF MILITARY IMPORTANCE: VACCINE ISSUES IN THE U.S. MILITARY
STANLEY M. LEMON, M.D. (Chair), Dean of Medicine and Professor,
University of Texas Medical Branch, Galveston
CHARLES C. J. CARPENTER, M.D., Professor of Medicine,
Brown University, and The Miriam Hospital, Providence, Rhode Island
CIRO A. de QUADROS, M.D., M.P.H., Director,
Division of Vaccines and Immunizations, Pan American Health Organization, Washington, D.C.
R. GORDON DOUGLAS, Jr., M.D.,
Princeton, New Jersey
LAWRENCE O. GOSTIN, J.D., LL.D. (Hon.), Codirector,
Georgetown/ Johns Hopkins Joint Program in Public Health and Law, and
Professor of Law,
Georgetown University, Washington, D.C.
M. CAROLYN HARDEGREE, M.D.,
SAMUEL L. KATZ, M.D., Wilburt C. Davison Professor and Chairman Emeritus,
Duke University Medical Center, Durham, North Carolina
F. MARC LaFORCE, M.D., Director,
Meningitis Vaccine Project, Program for Appropriate Technology in Health, Ferney-Voltaire, France
STANLEY A. PLOTKIN, M.D.,
GREGORY A. POLAND, M.D., Chief,
Mayo Vaccine Research Group, Mayo Clinic and Foundation, Rochester, Minnesota
N. REGINA RABINOVICH, M.D., M.P.H., Director,
Malaria Vaccine Initiative, Program for Appropriate Technology in Health, Rockville, Maryland
PHILIP K. RUSSELL, M.D., Special Advisor on Vaccine Development and Production,
Office of Public Health Preparedness, Department of Health and Human Services, Washington, D.C.
RONALD J. SALDARINI, Ph.D.,
Mahwah, New Jersey
MARY E. WILSON, M.D., Chief of Infectious Diseases,
Mount Auburn Hospital,
and Associate Professor of Medicine,
Harvard Medical School, Cambridge, Massachusetts
SUSAN THAUL, Ph.D., Study Director
SALEM FISSEHA, Research Assistant
RICHARD N. MILLER, M.D., M.P.H., Director,
Medical Follow-up Agency
HEATHER O’MAONAIGH, M.A., Program Officer
PAMELA RAMEY-McCRAY, Administrative Assistant
In April 2000, the Institute of Medicine (IOM) of the National Academies convened an expert committee to advise the U.S. Army Medical Research and Materiel Command on the management of its vaccine research programs for the protection of U.S. military personnel against naturally occurring infectious disease threats. The charge to the committee focused on the army’s Military Infectious Diseases Research Program and how it goes about its task of making available to the military new vaccines for the protection of warfighters against these constantly changing and emerging disease threats. That charge required the committee to examine broadly the process that the Department of Defense (DoD) uses to acquire and maintain the availability of vaccines. Doing so, the committee recognized that this process is too fragmented, too diffused, and too lacking in consolidation of its authority within a single responsible locus in DoD to operate efficiently and to be effective in meeting its critical mission. This report, the final product of the IOM Committee on a Strategy for Minimizing the Impact of Naturally Occurring Infectious Diseases of Military Importance: Vaccine Issues in the U.S. Military, details those findings as well as the information that was provided to the committee and that led it to reach these conclusions.
At the time that this report is being prepared for publication, the world is very different from the way it was 2 years earlier when the committee first convened. The terrorist attacks of September 11, 2001, and the subsequent mailing of lethally weaponized anthrax spores to members of the media and the U.S. Congress in the weeks that followed have forever altered the nation’s sense of its vulnerability to terrorism in general and to the possibility of the intentional dissemination of potentially fatal infectious diseases in particular. These events have led to the proposal of enormous increases in the funding for infectious disease
research, focused on biodefense, but certain to have significant spillover into the area of naturally transmitted infections. These new funds may answer, in whole or in part, one of the recommendations of this committee: that DoD substantially increase its budgetary support for infectious disease research and vaccine acquisition if it is to provide the protections required for the nation’s warfighters in an increasingly complex and dangerous world.
However, DoD’s interest in solving the problems with vaccine acquisition predated the events of September 11. Two important factors led to this growing concern over the functioning of vaccine acquisition efforts within DoD: (1) the awareness that the approach mandated by Congress for the development of countermeasures for biological warfare, the Joint Vaccine Acquisition Program, was failing to produce the vaccine products required and (2) the sudden loss from DoD’s armamentarium of the very successful vaccine that DoD had previously developed for the prevention of adenovirus serotype 4 and 7 disease in military recruits. These events led the Deputy Secretary for Defense to commission a separate study and report shortly after the creation of this IOM committee. That committee, chaired by Franklin Top, Jr., addressed many issues that overlapped the issues that this committee was charged to address.
Although its contents were unknown to this committee for many months, the Report on Biological Warfare Defense Vaccine Research and Development Programs, through which DoD released the Top Report1 to the public, ultimately presented conclusions very similar to those arrived at by this committee.
As explained in the pages that follow, this committee strongly believes that a full-fledged reorganization of DoD’s priority-setting and vaccine acquisition processes will be required if the department is to fulfill its pledge to protect U.S. warfighters against vaccine-preventable infectious diseases. It believes that this is an issue of national security, inasmuch as infectious diseases have well-proven abilities to significantly degrade and compromise the operations of military forces. The major limitations, it believes, in making available safe and efficacious vaccines for the protection of forces have not been scientific in nature but, rather, revolve around problems of organization, management, and budgetary support.
Where possible, the committee has cited substantive data and evidence in support of these conclusions. In many instances, however, such hard data have simply not been available and the committee has had to draw on the past experiences and perceptions of its members, individuals who have spent their careers at the highest points of leadership in military research and development programs,
Vaccine Study Panel. Department of Defense Acquisition of Vaccines Program: A Report to the Deputy Secretary of Defense from the Independent Panel of Experts, December 2000). In DoD 2001d. Report on Biological Warfare Defense Vaccine Research and Development Programs. Washington, DC: Department of Defense. [Online]. Available: http://www.defenselink.mil/pubs/ReportonBiologicalWarfareDefenseVaccineRDPrgras-July2001.pdf [accessed September 7, 2001].
the commercial vaccine industry, regulatory agencies, and academic infectious disease-related research and development communities.
The committee perceives with particular concern that the technology base and basic research activities of DoD are much narrower and limited in scope than they were in past decades, reflecting reductions in the numbers of military professional personnel, reductions in underlying budget support, and changes in program priorities. Although these trends are very difficult to document across the tens of years and the different military organizational structures that have evolved over time, none of the evidence that the committee reviewed refutes this belief. The committee believes that the technology base resides at the core of DoD’s capacity to meet its mission in protecting U.S. warfighters against infectious disease threats. Its erosion should be a matter of national concern, and one that must be reversed through a sustained commitment of budget and personnel as the nation enters the twenty-first century.
To accomplish the task for which it convened this committee, IOM recognized that committee membership must include individuals with considerable expertise and experience in pharmaceutical research, development, and manufacturing. IOM found it impossible to recruit individuals with such backgrounds who do not also hold significant amounts of equity in the industry. IOM chose retired industry experts to minimize the potential conflict of interest. Committee members R. Gordon Douglas, Jr., Stanley A. Plotkin, and Ronald J. Saldarini each own significant stock and stock option holdings in pharmaceutical companies that are involved in vaccine development and manufacture. Their biographical summaries (included in Appendix C) illustrate the invaluable experience that they brought to this committee’s work. At the first committee meeting, the Deputy Executive Officer of IOM conducted the required bias and conflict-of-interest discussion. All committee members were apprised of the points-of-view, experiences, and current activities of these committee members, as of all committee members, and were alerted to potential conflicts of interests. The vaccine manufacture section of Chapter 4 boldly presents a pharmaceutical industry view of the issues and labels it as such. The whole committee—aware of the source of advice—uniformly agreed with the analysis. It is my firm opinion that this judicious use of committee members whose potential conflicts of interest would ordinarily preclude their serving on IOM committees has been outstandingly successful and has served this committee and its sponsor well. The committee gained substantively from the experiences of those who have been close to commercial vaccine manufacture in the past, while it maintained its integrity by placing known biases and conflicts of interest on the table during discussions and also drawing heavily on the past experiences of other committee members in the regulation of vaccines and in both public and private vaccine development efforts.
Stanley M. Lemon, M.D.
This project had a scope that included laboratory procedures and personnel; protection of human subjects in research; federal regulation; organizational design and management; financing; history; military operational readiness; political, military, and public health intelligence; vaccinology; and the study, prevention, and treatment of infectious diseases worldwide. Individual committee members are recognized experts in many of these fields, but all of them—and the study staff—needed education to introduce, review, or update areas in which they were less involved. For this education, we turned to people in DoD, FDA, CDC, NIH, and the vaccine industry, along with other colleagues. Appendix B contains the agenda listings from committee meeting open sessions; the invited presenters listed there shared a lot of information and perspective with the committee and staff. We thank them. Some information required staff pursuit by telephone, e-mail, and fax. Thanks are due to Dr. Kathryn Zoon and her colleagues Bette Goldman, Dr. Karen Midthun, and Loni Warren at FDA; Drs. Ellen Boudreau, Mark Kortepeter, and Phillip Pittman at USAMRIID; COL John Frazier Glenn and William Howell at USAMRMC; Dr. John Brundage, WRAIR; Dr. Francis E. Cole, Jr., JVAP; and Michael A. Paysan, Jr., Requirements and Acquisition Division, Joint Staff, Pentagon.
The recipient of the bulk of our requests for information was our sponsor representative COL Charles H. Hoke, Jr., director of the Military Infectious Diseases Research Program at USAMRMC through the core of the IOM project. He and his colleagues Drs. Lawrence Lightner and Rodney Michael fielded our questions through hundreds of e-mails, telephone calls and voice-mail messages, and perhaps a dozen in-person meetings. COL Hoke’s task was large and his efforts to convey the scope of his concern for the direction of DoD in infectious
diseases research, especially vaccine-related work, earned our respect. We greatly appreciate his efforts and those of his MIDRP colleagues. Thanks also to Peggy Nathan, MIDRP secretary-extraordinaire, whose resourcefulness we at times call upon for questions unrelated to this project.
Behind many great committee members are highly focused personal, administrative, or secretarial assistants. Over the last two years, we have relied on many and want to especially thank Deborah James and Denise Burrell for their work keeping us and our mail in touch with our committee chair, Dr. Stanley Lemon; three staffers at Mayo Clinic who relayed messages to and from Dr. Gregory Poland across the globe; Brenda Cole who did the same for Dr. Samuel Katz; and Grace Fries, who helped sort through Dr. Stanley Plotkin’s numerous commitments to IOM activities.
We did not take all of the changes that our contract copyeditor Michael Hayes suggested. But just knowing that he would be editing the draft report made us write better. We thank him for his detailed and very thoughtful work.
The report was made possible by many staff members within the National Academies. Our thanks go to all of you, especially financial associate Andrea Cohen; Clyde Behney, Jennifer Bitticks, Carlos Orr, Jennifer Otten, and Bronwyn Schrecker in ORAC; Linda Kilroy in the Office of Contracts and Grants; Janice Mehler for the Report Review Committee; and Estelle Miller and Sally Stanfield at the National Academy Press. You each stepped up to move this project and report through to completion. Salem Fisseha, Richard Miller, Heather O’Maonaigh, Pamela Ramey-McCray, and I get our names on the final report. Others within the Medical Follow-up Agency helped us and the committee, whether by re-reading a paragraph to assure us that it said what we meant, offering (or withholding) candy or caffeine, managing guest support at committee meetings, or lending a hand when they saw we could use one. Thank you to Phillip Bailey, Harriet Crawford, Jihad Daghmash, Jane Durch, Rick Erdtmann, Reine Homawoo, Lois Joellenbeck, Karen Kazmerzak (who helped officially and well with this committee’s interim letter report), William Page, Noreen Stevenson, and newcomer Laura Sivitz.
Finally, we acknowledge MG Lester Martinez-Lopez, USAMRMC commanding general, and COL David Vaughn, RAD1 director. They have stepped into their positions in time to receive this report; we thank them in advance for the time we anticipate they will give to the issues the IOM committee raises in this report.
Susan Thaul, Ph.D.
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 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 confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
DONALD S. BURKE, M.D., The Johns Hopkins University, Baltimore, Maryland
HENRY GRABOWSKI, Ph.D., Duke University, Durham, North Carolina
WILLIAM H. HABIG, Ph.D., Centocor, Inc., Malvern, Pennsylvania
BRUCE INNIS, M.D., GlaxoSmithKline Biologicals, Collegeville, Pennsylvania
CRAIG LLEWELLYN, M.D., M.P.H., MC USA COL (Ret.), Uniformed Services University of Health Sciences, Bethesda, Maryland
JACK MELLING, Ph.D., The Karl Landsteiner Institute, Vienna, Austria
FRANKLIN H. TOP, Jr., M.D., MedImmune, Inc., Gaithersburg, Maryland
MILTON C. WEINSTEIN, Ph.D., Harvard School of Public Health, Boston, Massachusetts
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recom-
mendations nor did they see the final draft of the report before its release. The review of this report was overseen by Robert M. Chanock, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Enriqueta C. Bond, Ph.D., Burroughs Wellcome Fund. Appointed by the Institute of Medicine and the National Research Council, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
Boxes, Figures, and Tables
U.S. Army hospital admissions during war,
Military infectious disease-related research, development, and acquisition activities: USAMRMC interfaces with army and Office of the Secretary of Defense organizations,
U.S. Army Medical Department organizational chart,
U.S. Army Medical Research and Materiel Command organizational chart,
Research and development path for vaccines,
Military infectious disease-related research, development, and acquisition activities: USAMRMC interfaces with army and Office of the Secretary of Defense organizations,
Historical Highlights in the Control of U.S. Military Infectious Diseases by Vaccines,
Major Infectious Disease Threats for Which There Were No Licensed Vaccines at the Time of Deployments and Overseas Exercises,
USAMRMC Infectious Disease-Related Research Funding, FY 2002,
Selected Current Vaccine-Related Agreements,
Status of Vaccines for Specific Infectious Disease Threats to the U.S. Military,
FDA-Licensed Vaccines and Related Biologics Available to U.S. Military Personnel,
Selected Vaccines Previously Licensed by FDA but Not Available,
Vaccines Available to U.S. Military Personnel as IND Products,
Vaccines Administered as INDs That Are No Longer Being Produced and That Are of Limited Availability,
USAMRMC Fiscal Year 2001 Program Priorities, in Decreasing JTCG-2– Assigned Rank, and FY 2000 Investment in Exploratory Research,
FDA-Licensed Vaccines Used by SIP as of March 2002,
Vaccines with IND Status Used by SIP as of March 2002,
Vaccines with CDC-Sponsored IND Status Administered by SIP,
History of Funding for Science and Technology Base Through the USAMRMC Research Area Directorate for Infectious Diseases, FYs 1994 to 2002,
Abbreviations and Acronyms
Armed Forces Epidemiological Board
Army Medical Department
Assistant Secretary of the Army for Acquisition, Logistics, and Technology
Armed Services Biomedical Research, Evaluation and Management (Committee)
Assistant Secretary of Defense for Health Affairs
Biological Safety Level
Centers for Disease Control and Prevention
Cooperative Research and Development Agreement
Department of Health and Human Services
Department of Defense
Defense Supply Center, Philadelphia
Defense Technology Objective
Dual-Use Science and Technology
enterotoxigenic Escherichia coli
Food and Drug Administration
Force Health Protection
Future Operational Capability
General Accounting Office
government-owned, contractor-operated (manufacturing facility)
hepatitis E virus
human immunodeficiency virus
investigational new drug
Institute of Medicine
Joint Technology Coordinating Group-2
Joint Vaccine Acquisition Program
Joint Working Group
U.S. Army Medical Command
Military Infectious Diseases Research Program
Navy Medical Research Unit 2
National Intelligence Council
National Institutes of Health
Operational Requirements Document
Office of the Secretary of Defense
Research Area Directorate
research, development, and acquisition
Special Immunizations Program
Science and Technology Evaluation Program
Science and Technology Objective
U.S. Army Training and Doctrine Command
The Salk Institute, Government Services Division
U.S. Army Medical Materiel Agency
U.S. Army Medical Materiel Development Activity
U.S. Army Medical Research Acquisition Activity
U.S. Army Medical Research Institute of Infectious Diseases
U.S. Army Medical Research and Materiel Command