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Anna Nicholson, Rebecca A. English, Rita S. Guenther, and
Anne B. Claiborne, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Board on Health Sciences Policy
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The workshop that is the subject of this workshop summary was
approved by the Governing Board of the National Research Council, whose mem-
bers are drawn from the councils of the National Academy of Sciences, the National
Academy of Engineering, and the Institute of Medicine.
This activity was supported by contracts between the National Academy of Sciences
and Department of Health and Human Services (Contract Nos. N01-OD-4-2139
and HHSF223001003T), Abbott Pharmaceuticals, American Diabetes Association,
American Society for Microbiology, Amgen Inc., Association of American Medical
Colleges, Bristol-Myers Squibb, Burroughs Wellcome Fund, Celtic Therapeutics,
LLLP, Critical Path Institute, Doris Duke Charitable Foundation, Eli Lilly and Com-
pany, Eli Lilly & Co. Foundation, FasterCures, Foundation for the NIH, Friends of
Cancer Research, GlaxoSmithKline, Janssen Research & Development, LLC, March
of Dimes Foundation, Merck & Co., Inc., Novartis Pharmaceuticals Corporation,
and Pfizer Inc. The views presented in this publication do not necessarily reflect the
views of the organizations or agencies that provided support for the activity.
International Standard Book Number-13: 978-0-309-26595-9
International Standard Book Number-10: 0-309-26595-9
Additional copies of this workshop summary are available for sale from the National
Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800)
624-6242 or (202) 334-3313; http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page
at: www.iom.edu.
Copyright 2013 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
The serpent has been a symbol of long life, healing, and knowledge among almost
all cultures and religions since the beginning of recorded history. The serpent
adopted as a logotype by the Institute of Medicine is a relief carving from ancient
Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2013. Developing and Strengthen-
ing the Global Supply Chain for Second-Line Drugs for Multidrug-Resistant Tuber-
culosis: Workshop Summary. Washington, DC: The National Academies Press.
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“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
Advising the Nation. Improving Health.
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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 Acad-
emy 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
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sharing with the National Academy of Sciences the responsibility for advising the
federal government. The National Academy of Engineering also sponsors engineer-
ing programs aimed at meeting national needs, encourages education and research,
and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi-
dent 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 Insti-
tute 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
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Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sci-
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Functioning in accordance with general policies determined by the Academy, the
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cil 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
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PLANNING COMMITTEE FOR THE WORKSHOP
ON GLOBAL DRUG SUPPLY CHAIN FOR SECOND-
LINE ANTI-TUBERCULOSIS DRUGS1
BARRY R. BLOOM (Co-Chair), Harvard School of Public Health,
Boston, MA
GAIL H. CASSELL (Co-Chair), Harvard Medical School (Visiting),
Carmel, IN
RIFAT ATUN, Imperial College Business School, Imperial College
London, England
PETER CEGIELSKI, U.S. Centers for Disease Control and Prevention,
Atlanta, GA
LUCICA DITIU, Stop TB Partnership, World Health Organization,
Geneva, Switzerland
GARY L. FILERMAN, Atlas Health Foundation, McLean, VA
HELLEN GELBAND, Center for Disease Dynamics, Economics & Policy,
Inc., Washington, DC
MARK J. GOLDBERGER, Abbott Pharmaceuticals, Rockville, MD
DOUGLAS L. KEENE, Management Sciences for Health, Arlington, VA
SALMAAN KESHAVJEE, Harvard Medical School, Boston, MA
MONTSERRAT MEIRO-LORENZO, World Bank, Washington, DC
ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation,
New York, NY
PAUL P. NUNN,2 World Health Organization, Geneva, Switzerland
ARIEL PABLOS-MÉNDEZ, United States Agency for International
Development, Washington, DC
TRACY J. SIMS, Eli Lilly & Co. Foundation, Indianapolis, IN
BRENDA WANING, UNITAID, World Health Organization, Geneva,
Switzerland
PRASHANT YADAV, University of Michigan, Ann Arbor
IOM Staff
ANNE B. CLAIBORNE, Forum Director
RITA S. GUENTHER, Program Officer
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
1 Institute
of Medicine planning committees are solely responsible for organizing the work-
shop, identifying topics, and choosing speakers. The responsibility for the published workshop
summary rests with the workshop rapporteurs and the institution.
2 Paul Nunn was with the World Health Organization during the planning of the workshop.
v
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FORUM ON DRUG DISCOVERY,
DEVELOPMENT, AND TRANSLATION1
JEFFREY M. DRAZEN (Co-Chair), New England Journal of Medicine,
Boston, MA
STEVEN K. GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA
MARGARET ANDERSON, FasterCures, Washington, DC
HUGH AUCHINCLOSS, National Institute of Allergy and Infectious
Diseases, Bethesda, MD
CHRISTOPHER AUSTIN, National Center for Advancing Translational
Sciences, Bethesda, MD
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
C. THOMAS CASKEY, Baylor College of Medicine, Houston, TX
GAIL H. CASSELL, Harvard Medical School (Visiting), Carmel, IN
PETER B. CORR, Celtic Therapeutics, LLLP, New York, NY
ANDREW M. DAHLEM, Eli Lilly and Company, Indianapolis, IN
TAMARA DARSOW, American Diabetes Association, Alexandria, VA
JAMES H. DOROSHOW, National Cancer Institute, Bethesda, MD
GARY L. FILERMAN, Atlas Health Foundation, McLean, VA
GARRET A. FITZGERALD, University of Pennsylvania School of
Medicine, Philadelphia
MARK J. GOLDBERGER, Abbott Pharmaceuticals, Rockville, MD
HARRY B. GREENBERG, Stanford University School of Medicine, CA
STEPHEN GROFT, National Center for Advancing Translational
Sciences, Bethesda, MD
LYNN HUDSON, Critical Path Institute, Tucson, AZ
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 Inc., 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.
vii
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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, Washington, DC
ELLIOTT SIGAL, Bristol-Myers Squibb, Princeton, NJ
ELLEN R. STRAHLMAN, GlaxoSmithKline, Research Triangle Park, NC
NANCY SUNG, Burroughs Wellcome Fund, Research Triangle Park, NC
JANET TOBIAS, Ikana Media and Mount Sinai School of Medicine,
New York, NY
JOANNE WALDSTREICHER, Janssen Research & Development, LLC,
Raritan, NJ
JANET WOODCOCK, Food and Drug Administration, White Oak, MD
IOM Staff
ANNE B. CLAIBORNE, Forum Director
RITA S. GUENTHER, Program Officer
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
viii
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Reviewers
This workshop summary has been reviewed in draft form by individu-
als chosen for their diverse perspectives and technical expertise, in accor-
dance 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 the
workshop summary 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 workshop
summary:
Colin Boyle, University of California, San Francisco, Global Health
Sciences
Jennifer Furin, Case Western Reserve University School of Medicine
Robert Matiru, UNITAID
Owen Robinson, Partners In Health
Although the reviewers listed above have provided many constructive
comments and suggestions, they did not see the final draft of the workshop
summary before its release. The review of this workshop summary was
overseen by Enriqueta C. Bond, QE Philanthropic Advisors. Appointed
by the Institute of Medicine, she was responsible for making certain that
an independent examination of this workshop summary was carried out
in accordance with institutional procedures and that all review comments
were carefully considered. Responsibility for the final content of this work-
shop summary rests entirely with the rapporteurs and the institution.
ix
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Contents
ACRONYMS xv
1 INTRODUCTION 1
Background and History of the Current GLC Mechanism, 4
Principles of Drug Supply Chains, 12
Barriers, Challenges, and Needs, 18
2 LOGISTICS, SUPPLY, AND DEMAND 49
Quality Assurance, 49
Forecasting and Information Management, 56
Drug Shortages, 62
3 FINANCING OF MDR TB SLDs 67
Funding of the MDR TB Supply Chain, 67
Models for Financing and Supply, 76
4 INNOVATIVE SUGGESTIONS AND POTENTIAL SOLUTIONS 93
Mechanisms of Purchase and Supply, 93
Logistics, Supply, and Demand, 99
Innovative Financing, 103
Reflecting on the Way Forward, 106
REFERENCES 111
xi
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xii CONTENTS
APPENDIXES
A WORKSHOP AGENDA 115
B PARTICIPANT BIOGRAPHIES 129
C REGISTERED WORKSHOP ATTENDEES 149
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Table, Figures, and Boxes
TABLE
1-1 SLD Supply Chain Stakeholders: Responsibilities, Interests, and
Barriers, 26
FIGURES
1-1 Number of GLC pilot projects implemented around the world
between 2000 and 2009, 10
1-2 Creation of a centralized node of control for the GLC-approved
SLD supply chain, 11
1-3 Existing supply chain for SLDs, 14
1-4 A “buffer” supply of SLDs smoothens the lumpiness of
demand, 16
1-5 Shifting the push-pull boundary in the SLD supply chain, 17
1-6 The current structure of supply and demand works against the
goals of affordable and sustainable access, 19
1-7 Key barriers to improving SLD access: high prices and limited
availability of QA MDR TB drugs, 20
1-8 The GLC initiative flow through cycle, 21
1-9 Of the estimated 5 million MDR TB cases that occurred between
2000 and 2009, only 0.2–0.5 percent were treated in GLC-
approved programs, 23
1-10 Push and pull mechanisms for adopting innovations for
MDR TB, 29
xiii
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xiv TABLE, FIGURES, AND BOXES
1-11 Regulatory steps from drug development to delivery, 32
1-12 GDF procurement cycle, 34
2-1 WHO PQ second-line medicines as of the July 2012, IOM
workshop, 51
3-1 Global TB drug pipeline, as of June 18, 2012, 73
3-2 Global Fund product classification framework proposed by Results
for Development Institute (R4D), 83
3-3 Price benefits of splitting tenders, 86
3-4 SLDAII vision and goals, 88
3-5 Owner/participant teams for the top five MDR TB Innovation
Summit ideas, 91
BOXES
1-1 Key Drug Supply Chain Themes from Previous IOM Forum
Publications, 4
1-2 Statement of Task for the Workshop, 6
1-3 Cycloserine Case Study, 18
1-4 Country Approaches to the MDR TB SLD Supply Chain, 43
1-5 Suggested Ways Forward, 46
2-1 Considering Two Key Priorities in the Donor-Funded MDR TB
Market: QA and Treatment Access, 58
3-1 Related Efforts in SLD Supply Chain and Access, 88
4-1 Suggestions and Low-Hanging Fruit, 109
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Acronyms
ACT artemisinin-combination therapy
AIDS acquired immune deficiency syndrome
AMC advance market commitment
AMFm Affordable Medicines Facility-malaria
AMRH African Medicines Regulatory Harmonization
APC advance purchase commitment
API active pharmaceutical ingredient
ARV antiretroviral
BMGF Bill & Melinda Gates Foundation
BRICS Brazil, Russia, India, China, and South Africa
CDC U.S. Centers for Disease Control and Prevention
CHAI Clinton Health Access Initiative
DOT directly observed treatment
DOTS Directly Observed Treatment-Short course
DR TB drug-resistant tuberculosis
DST drug susceptibility testing
EMA European Medicines Agency
EMR electronic medical record
FDA U.S. Food and Drug Administration
FLD first-line anti-TB drug
xv
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xvi ACRONYMS
FPP finished pharmaceutical product
GDF Global Drug Facility
GHC Global Health Committee
GLC Green Light Committee
HCP health care professional
HIV human immunodeficiency virus
ICH International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for
Human Use
IFFIm International Finance Facility for Immunization
IOM Institute of Medicine
IQA internationally quality-assured
MDR TB multidrug-resistant tuberculosis
MSF Médecins Sans Frontières
MSH Management Sciences for Health
M.tb. Mycobacterium tuberculosis
NGO nongovernmental organization
NRA national regulatory authority
NTP national TB control programme
OpenMRS Open Medical Record System
PAS 4-aminosalicylic acid
PEPFAR U.S. President’s Emergency Plan for AIDS Relief
PMDT programmatic management of drug-resistant tuberculosis
PQ prequalified (by WHO)
PRI Program-Related Investment
QA quality-assured/quality assurance
QC quality control
SCM supply chain management
SCMS Supply Chain Management System (PEPFAR/USAID)
SLD second-line anti-TB drug
SLDAII Second-Line Drug Access Improvement Initiative
SMS short message service
SRA stringent regulatory authority
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ACRONYMS xvii
TB tuberculosis
UNICEF United Nations Children’s Fund
USAID United States Agency for International Development
USP U.S. Pharmacopeial Convention
WHO World Health Organization
WHO PQ WHO prequalification
WHO PQP WHO Prequalification of Medicines Programme
XDR TB extensively drug-resistant tuberculosis
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