Developing and Strengthening
the Global Supply Chain
for Second-Line Drugs for
Multidrug-Resistant Tuberculosis

WORKSHOP SUMMARY

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

INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.

www.nap.edu

NOTICE: The workshop that is the subject of this workshop summary 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 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 Company, 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

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Suggested citation: IOM (Institute of Medicine). 2013. Developing and Strengthening the Global Supply Chain for Second-Line Drugs for Multidrug-Resistant Tuberculosis: Workshop Summary. Washington, DC: The National Academies Press.

“Knowing is not enough; we must apply.
Willing is not enough; we must do.”

—Goethe

INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine

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.

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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.

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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 workshop, 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.

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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.

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

Reviewers

This workshop summary 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 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 workshop summary rests entirely with the rapporteurs and the institution.

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Contents

ACRONYMS

1        INTRODUCTION

Background and History of the Current GLC Mechanism

Principles of Drug Supply Chains

Barriers, Challenges, and Needs

2        LOGISTICS, SUPLY, AND DEMAND

Quality Assurance

Forecasting and Information Management

Drug Shortages

3        FINANCING OF MDR TB SLDS

Funding of the MDR TB Supply Chain

Models for Financing and Supply

4        INNOVATIVE SUGGESTIONS AND POTENTIAL SOLUTIONS

Mechanisms of Purchase and Supply

Logistics, Supply, and Demand

Innovative Financing

Reflecting on the Way Forward

REFERENCES

APPENDIXES

A        Workshop Agenda

B        Participant Biographies

C        Registered Workshop Attendees

Table, Figures, and Boxes

TABLE

1-1      SLD Supply Chain Stakeholders: Responsibilities, Interests, and Barriers

FIGURES

1-1      Number of GLC pilot projects implemented around the world between 2000 and 2009

1-2      Creation of a centralized node of control for the GLC-approved SLD supply chain

1-3      Existing supply chain for SLDs

1-4      A “buffer” supply of SLDs smoothens the lumpiness of demand

1-5      Shifting the push-pull boundary in the SLD supply chain

1-6      The current structure of supply and demand works against the goals of affordable and sustainable access

1-7      Key barriers to improving SLD access: high prices and limited availability of QA MDR TB drugs

1-8      The GLC initiative flow through cycle

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

1-10    Push and pull mechanisms for adopting innovations for MDR TB

1-11    Regulatory steps from drug development to delivery

1-12    GDF procurement cycle

2-1      WHO PQ second-line medicines as of the July 2012, IOM workshop

3-1      Global TB drug pipeline, as of June 18, 2012

3-2      Global Fund product classification framework proposed by Results for Development Institute (R4D)

3-3      Price benefits of splitting tenders

3-4      SLDAII vision and goals

3-5      Owner/participant teams for the top five MDR TB Innovation Summit ideas

BOXES

1-1      Key Drug Supply Chain Themes from Previous IOM Forum Publications

1-2      Statement of Task for the Workshop

1-3      Cycloserine Case Study

1-4      Country Approaches to the MDR TB SLD Supply Chain

1-5      Suggested Ways Forward

2-1      Considering Two Key Priorities in the Donor-Funded MDR TB Market: QA and Treatment Access

3-1      Related Efforts in SLD Supply Chain and Access

4-1      Suggestions and Low-Hanging Fruit

Acronyms

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