ADVANCING REGULATORY SCIENCE
FOR MEDICAL COUNTERMEASURE
DEVELOPMENT
Workshop Summary
Theresa Wizemann, Bruce M. Altevogt, and
Anne B. Claiborne, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Forum on Medical and Public Health Preparedness
for Catastrophic Events
Board on Health Sciences Policy
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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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.
This project was supported by contracts between the National Academy of Sciences and Department of Health and Human Services (Contract Nos. N01-OD-4-2139 TO #158, HHSF223001003T, HHSF22301022T TO #24, N01-OD-4-2139 TO #198, HHSP233200900680P, HH5P23320042509X1, and HHSP233200800498P), the American Diabetes Association, the American Society for Microbiology, Amgen Inc., the Association of American Medical Colleges, Bristol-Myers Squibb, the Burroughs Wellcome Fund, Celtic Therapeutics, LLLP, the Critical Path Institute, the Doris Duke Charitable Foundation, Eli Lilly & Co., FasterCures, the Foundation for the NIH, Friends of Cancer Research, GlaxoSmithKline, Howard Hughes Medical Institute, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer, Inc, the American College of Emergency Physicians, the American Hospital Association, the American Medical Association, the American Nurses Association, the Association of State and Territorial Health Officials, the Centers for Disease Control and Prevention (Contract No. 200-2005-13434 TO #6), the Department of the Army (Contract No. W81XWH-08-P-0934), the Department of Homeland Security’s Office of Health Affairs (Contract No. HSHQDC-07-C-00097), the Department of Homeland Security, Federal Emergency Management Agency (Contract No. HSFEHQ-08-P-1800), the Department of Transportation’s National Highway Traffic Safety Administration (DTNH22-10-H-00287) the Department of Veterans Affairs (Contract No. V101(93)P-2136 TO #10), the Emergency Nurses Association, the National Association of Chain Drug Stores, the National Association of County and City Health Officials, the National Association of Emergency Medical Technicians, the Pharmaceutical Research and Manufacturers of America, The Robert Wood Johnson Foundation, and the United Health Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-21490-2
International Standard Book Number-10: 0-309-21490-4
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Suggested citation: IOM (Institute of Medicine). 2011. Advancing Regulatory Science for Medical Countermeasure Development: Workshop Summary. Washington, DC: The National Academies Press.
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OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
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PLANNING COMMITTEE FOR THE WORKSHOP ON ADVANCING REGULATORY SCIENCE FOR MEDICAL COUNTERMEASURE DEVELOPMENT1
LESLIE Z. BENET (Co-Chair), University of California-San Francisco
JOHN REX, (Co-Chair), AstraZeneca, Waltham, MA
MARGARET ANDERSON, FasterCures, Washington, DC
PHYLLIS ARTHUR, Biotechnology Industry Organization, Washington, DC
ANTHONY BAHINSKI, Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA
LUCIANA BORIO, Food and Drug Administration, Silver Spring, MD
GAIL H. CASSELL, Harvard Medical School (visiting), Carmel, IN
GARRET A. FITZGERALD, University of Pennsylvania School of Medicine, Philadelphia
STEVEN K. GALSON, Amgen Inc., Thousand Oaks, CA
JOHN GRABENSTEIN, Merck & Co., Inc., West Point, PA
ROBERT KADLEC, PRTM Management Consultants, Washington, DC
MICHAEL KATZE, University of Washington, Seattle, WA
GEORGE KORCH, Department of Health and Human Services, Washington, DC
MICHAEL KURILLA, National Institute of Allergy and Infectious Diseases, Bethesda, MD
BERNARD MUNOS, InnoThink, Indianapolis, IN
GERALD PARKER, Department of Defense, Washington, DC
MARY PENDERGAST, Pendergast Consulting, Washington, DC
NICKI PESIK, Centers for Disease Control and Prevention, Atlanta, GA
ERIC TONER, Center for Biosecurity of the UPMC, Baltimore, MD
IOM Staff
ANNE B. CLAIBORNE, Director, Forum on Drug Discovery, Development, and Translation
BRUCE M. ALTEVOGT, Director, Forum on Medical and Public Health Preparedness for Catastrophic Events
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
DONNA L. RANDALL, Administrative Assistant
ROBIN GUYSE, Senior Program Assistant
ALEX REPACE, Senior Program Assistant
_____________
1 Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
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FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
GAIL H. CASSELL (Co-Chair), Harvard Medical School (visiting), Carmel, IN
JEFFREY M. DRAZEN (Co-Chair), New England Journal of Medicine, Boston, MA
BARBARA ALVING, National Center for Research Resources, Bethesda, MD
MARGARET ANDERSON, FasterCures, Washington, DC
LESLIE Z. BENET, University of California-San Francisco
ANN BONHAM, Association of American Medical Colleges, Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, MD
ROBERT CALIFF, Duke University Medical Center, Durham, NC
SCOTT CAMPBELL, Foundation for the National Institutes of Health, Bethesda, MD
C. THOMAS CASKEY, University of Texas-Houston Health Science Center
PETER B. CORR, Celtic Therapeutics, LLLP, New York, NY
ANDREW M. DAHLEM, Eli Lilly and Company, Indianapolis, IN
JAMES H. DOROSHOW, National Cancer Institute, Bethesda, MD
GARY L. FILERMAN, ATLAS Research, McLean, VA
GARRET A. FITZGERALD, University of Pennsylvania School of Medicine, Philadelphia
ELAINE K. GALLIN, QE Philanthropic Advisors, Potomac, MD
STEVEN K. GALSON, Amgen Inc., Thousand Oaks, CA
HARRY B. GREENBERG, Stanford University School of Medicine, Stanford, CA
STEPHEN GROFT, National Institutes of Health, Bethesda, MD
ANNALISA JENKINS, Bristol-Myers Squibb, Plainsboro, NJ
MICHAEL KATZ, March of Dimes Foundation, White Plains, NY
PETRA KAUFMANN, National Institute of Neurological Disorders and Stroke, Bethesda, MD
JACK D. KEENE, Duke University Medical Center, Durham, NC
RONALD L. KRALL, University of Pennsylvania, Center for Bioethics, Steamboat Springs, CO
FREDA LEWIS-HALL, Pfizer, New York, NY
MARK B. McCLELLAN, The Brookings Institution, Washington, DC
CAROL MIMURA, University of California-Berkeley
_____________
1 Institute of Medicine forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation, New York, NY
JOHN ORLOFF, Novartis Pharmaceuticals Corporation, East Hanover, NJ
AMY PATTERSON, National Institutes of Health, Bethesda, MD
MICHAEL ROSENBLATT, Merck & Co., Inc., Whitehouse Station, NJ
JANET SHOEMAKER, American Society for Microbiology, Washington, DC
ELLEN SIGAL, Friends of Cancer Research, Arlington, VA
ELLEN STRAHLMAN, GlaxoSmithKline, Research Triangle Park, NC
NANCY SUNG, Burroughs Wellcome Fund, Research Triangle Park, NC
JORGE A. TAVEL, National Institute of Allergy and Infectious Diseases, Bethesda, MD
JANET TOBIAS, Mt. Sinai School of Medicine, New York, NY
JOANNE WALDSTREICHER, Johnson & Johnson, Raritan, NJ
JANET WOODCOCK, Food and Drug Administration, White Oak, MD
RAYMOND L. WOOSLEY, The Critical Path Institute, Tucson, AZ
IOM Staff
ANNE B. CLAIBORNE, Forum Director
REBECCA A. ENGLISH, Associate Program Officer
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ROBIN GUYSE, Senior Program Assistant
FORUM ON MEDICAL AND PUBLIC HEALTH PREPAREDNESS FOR CATASTROPHIC EVENTS1
ROBERT KADLEC (Co-Chair), PRTM Management Consultants, Washington, DC
LYNNE KIDDER (Co-Chair), Center for Excellence in Disaster Management and Humanitarian Assistance, Tripler AMC, Hawaii
ALEX ADAMS, National Association of Chain Drug Stores Foundation, Alexandria, VA
DAMON ARNOLD, Association of State and Territorial Health Officials, Arlington, VA
GEORGES BENJAMIN, American Public Health Association, Washington, DC
VICTORIA DAVEY, Department of Veterans Affairs, Washington, DC
JEFFREY DUCHIN, Seattle & King County and University of Washington, Seattle
ALEXANDER GARZA, Department of Homeland Security, Washington, DC
JULIE GERBERDING, Merck Vaccines, West Point, PA
LEWIS GOLDFRANK, New York University Medical Center, New York
DAN HANFLING, Inova Health System, Falls Church, VA
JACK HERRMANN, National Association of County and City Health Officials, Washington, DC
JAMES JAMES, American Medical Association, Chicago, IL
JERRY JOHNSTON, National Association of Emergency Medical Technicians, Mt. Pleasant, IA
BRIAN KAMOIE, The White House, Washington, DC
LISA KAPLOWITZ, HHS Office of the Assistant Secretary for Preparedness and Response, Washington, DC
ALI KHAN, Centers for Disease Control and Prevention, Atlanta, GA
MICHAEL KURILLA, National Institute of Allergy and Infectious Diseases, Bethesda, MD
JAYNE LUX, National Business Group on Health, Washington, DC
ANTHONY MACINTYRE, American College of Emergency Physicians, Washington, DC
ANGELA McGOWAN, Robert Wood Johnson Foundation, Princeton, NJ
MARGARET McMAHON, Emergency Nurses Association,
Williamstown, NJ
MATTHEW MINSON, Texas A&M University, College Station, TX
_____________
1 Institute of Medicine forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
ERIN MULLEN, Pharmaceutical Research and Manufacturers of America, Washington, DC
CHERYL PETERSON, American Nurses Association, Silver Spring, MD
STEVEN PHILLIPS, National Library of Medicine, Bethesda, MD
ROSLYNE SCHULMAN, American Hospital Association, Washington, DC
RICHARD SERINO, Federal Emergency Management Agency, Washington, DC
MICHAEL SKIDMORE, Office of Assistant Secretary of Defense for Health Affairs, Department of Defense, Washington, DC
SHARON STANLEY, American Red Cross, Washington, DC
ERIC TONER, University of Pittsburgh Medical Center, Pittsburgh, PA
REED TUCKSON, UnitedHealth Group, Minneapolis, MN
MARGARET VANAMRINGE, The Joint Commission, Washington, DC
GAMUNU WIEJETUNGE, National Highway Traffic Safety Administration, Washington, DC
IOM Staff
BRUCE M. ALTEVOGT, Forum Director
CLARE STROUD, Program Officer
KRISTIN VISWANATHAN, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ALEX REPACE, Senior Program Assistant
Reviewers
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 process. We wish to thank the following individuals for their review of this report:
Gigi Kwik Gronvall, Center for Biosecurity of UPMC
Richard Jaffe, ANSER/Analytic Services Inc.
Jon Mogford, Defense Sciences Office, DARPA
Raymond L. Woosley, The Critical Path Institute
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the final draft of the report before its release. The review of this report was overseen by Peter Honig, AstraZeneca. Appointed by the Institute of Medicine, he was 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 authors and the institution.
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Contents
Charge to the Workshop Participants
Implementing the 2010 PHEMCE Review
Overview of the FDA MCM Initiative
Summary of Key Workshop Themes
2 MCM ENTERPRISE AND STAKEHOLDER PERSPECTIVES
FDA Regulatory Science Research Needs
Enterprise Partner and Stakeholder Perspectives
3 CUTTING-EDGE EFFORTS TO ADVANCE MCM REGULATORY SCIENCE
Nonclinical Approaches to Assessing Efficacy
Safety and Real-Time Monitoring
Synthetic and Computational Biology and Platform Technologies
Tables, Figures, and Boxes
TABLES
2-1 Examples of Potential Areas for Pillar 2 Research in CDER
2-2 Examples of Potential Areas for Pillar 2 Research in CBER
3-1 Prediction of Clinical Outcomes: Preclinical Toxicology Studies vs. Clinical Studies
FIGURES
2-1 FDA regulatory review cycle
3-1 In silico modeling of disease mechanisms for drug development
3-2 Human tissue engineering as a potential tool for testing medicines in lieu of animal models
3-3 Mobile bioprocessing facilities (MBFs)
3-4 Synthesis of bacterial cells
3-5 Accelerating seasonal influenza virus vaccine development
ASPR |
HHS Assistant Secretary for Preparedness and Response |
BARDA |
Biomedical Advanced Research and Development Authority |
BUN |
blood urea nitrogen |
CBER |
FDA Center for Biologics Evaluation and Research |
CBRN |
chemical, biological, radiological, nuclear |
CDC |
Centers for Disease Control and Prevention |
CDER |
FDA Center for Drug Evaluation and Research |
CDISC |
Clinical Data Interchange Standards Consortium |
CDRH |
FDA Center for Devices and Radiological Health |
CNS |
central nervous system |
C-Path |
Critical Path Institute |
DARPA |
Defense Advanced Research Projects Agency |
DoD |
Department of Defense |
EUA |
emergency use authorization |
FDA |
U.S. Food and Drug Administration |
GLP |
good laboratory practice |
GMP |
good manufacturing practice |
HHS |
U.S. Department of Health and Human Services |
HL7 |
Health Level Seven International |
IND |
investigational new drug |
IOM |
Institute of Medicine |
IRB |
institutional review board |
LRN |
CDC Laboratory Response Network |
MBF |
mobile bioprocessing facility |
MCM |
medical countermeasure |
MIMIC |
Modular IMmune In Vitro Constructs |
MRSA |
methicillin-resistant Staphylococcus aureus |
NBSB |
National Biodefense Science Board |
NCTR |
FDA National Center for Toxicological Research |
NIAID |
National Institute of Allergy and Infectious Diseases |
NIH |
National Institutes of Health |
NRC |
National Research Council |
PCAST |
President’s Council of Advisors on Science and Technology |
PCR |
polymerase chain reaction |
PHEMCE |
Public Health Emergency Medical Countermeasures Enterprise |
PK/PD |
pharmacokinetic/pharmacodynamic |
PSTC |
Predictive Safety Testing Consortium |
RNA |
ribonucleic acid |
SNS |
Strategic National Stockpile |
VAERS |
Vaccine Adverse Event Reporting System |
VXDS |
Voluntary Exploratory Data Submission program |