Countering the Problem of
Falsified and Substandard Drugs
Committee on Understanding the Global Public Health Implications of
Substandard, Falsified, and Counterfeit Medical Products
Board on Global Health
Gillian J. Buckley and Lawrence O. Gostin, Editors
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW 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 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.
This study was supported by Contract No. HHSF22301024T, TO #25 between the National Academy of Sciences and the U.S. Food and Drug Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-26939-1
International Standard Book Number-10: 0-309-26939-3
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Suggested citation: IOM (Institute of Medicine). 2013. Countering the problem of falsified and substandard drugs. Washington, DC: The National Academies Press.
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.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president 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 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.
COMMITTEE ON UNDERSTANDING THE GLOBAL
PUBLIC HEALTH IMPLICATIONS OF SUBSTANDARD,
FALSIFIED, AND COUNTERFEIT MEDICAL PRODUCTS
LAWRENCE O. GOSTIN (Chair), the Linda and Timothy O’Neill Professor of Global Health Law; Director, WHO Collaborating Center on Public Health Law and Human Rights, Georgetown University Law Center, Washington, DC
DANIEL CARPENTER, Allie S. Freed Professor of Government, Harvard University, Cambridge, MA
HANS HOGERZEIL, Professor of Global Health, Groningen University, The Netherlands; Former Director, Essential Medicines and Pharmaceutical Policies, World Health Organization, Geneva, Switzerland
THOMAS P. LAYLOFF, Senior Quality Assurance Director, Supply Chain Management System, Arlington, VA
ANN MARIE KIMBALL, Senior Program Officer of Epidemiology and Surveillance, Bill & Melinda Gates Foundation, Seattle, WA
PATRICK LUKULAY, Director, Promoting the Quality of Medicines Program, U.S. Pharmacopeia, Rockville, MD
MARGARETH NDOMONDO-SIGONDA, Pharmaceutical Coordinator, New Partnership for Africa’s Development, Pretoria, South Africa
ARTI K. RAI, Elvin R. Latty Professor, Duke University School of Law, Durham, NC
MARCO ANTONIO STEPHANO, Professor, University of São Paulo, School of Pharmaceutical Sciences, Brazil
JOHN THERIAULT, Former Vice President of Security, Apple Inc., Cupertino, CA; Former Vice President of Security, Pfizer, Inc., New York, NY
MARY E. WILSON, Adjunct Associate Professor of Global Health and Population, Harvard University School of Public Health, Boston, MA
PRASHANT YADAV, Director, Healthcare Research, William Davidson Institute, University of Michigan, Ann Arbor
IOM Staff
GILLIAN BUCKLEY, Program Officer, Study Director
KENISHA PETERS, Research Associate
MEGAN GINIVAN, Research Assistant
KATHLEEN BURNS, Intern
JULIE WILTSHIRE, Financial Associate
PATRICK W. KELLEY, Director, Boards on Global Health and African Science Academy Development
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 deliberative process. We wish to thank the following individuals for their review of this report:
Georges Benjamin, American Public Health Association
Martha Brumfield, Martha A. Brumfield, LLC
Stephen Byrn, Purdue University
Philip Chen, formerly of Georgetown University Law Center
Charles Clift, Chatham House
Michael Greene, Centers for Disease Control and Prevention
William Greene, St. Jude Children’s Research Hospital
Noel Greis, University of North Carolina at Chapel Hill
Harparkash Kaur, London School of Hygiene and Tropical Medicine
Thomas Kubic, Pharmaceutical Security Institute
Joshua Sharfstein, Maryland Department of Health & Mental Hygiene
Marv Shepherd, University of Texas at Austin
Andy Stergachis, University of Washington
Chen Yang, Sidley Austin, LLP
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Harold Fallon, Medical University of South Carolina, and Elaine Larson, School of Nursing and Mailman School of Public Health, Columbia University. Appointed by the National Research Council and the Institute of Medicine, 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.
This report is a product of the cooperation and contributions of many people. The committee and staff are especially grateful to Danielle Turnipseed and Livia Navon for their work on the manuscript, and to Deepali Patel and Susan McCutchen for their fast and accurate reference review. The project ran smoothly because of the contributions of Jim Banihashemi, Sarah Ziegenhorn, Laura Harbold DeStefano, Anne Claiborne, and Vilija Teel of the Institute of Medicine. Janice Mehler of the Report Review Committee oversaw a careful peer review of the manuscript.
Many experts outside of the Academies helped the committee and staff with this project. Bryan Liang of the University of California, San Diego, was not able to serve on the committee but contributed to the first meeting. Michael Deats, Jitka Sabartova, and Sabine Kopp of the WHO shared their technical expertise; Tom Kubic of PSI, Inc. shared and explained his organization’s unpublished data; Vincent Ahonkai of the Bill & Melinda Gates Foundation, Kelly Catlin of CHAI, and James Droop and Saul Walker of DFID shared information about medicine procurement and quality assurance; Mark Paxton of the FDA explained RFID technology; Ashifi Gogo of Sproxil explained mobile verification; Mariam Khan of BMI shared pharmaceutical sales data; and Lynda Scammell of the MHRA shared her technical expertise.
Members of the committee and staff traveled to Brasília, Delhi, Geneva, Hyderabad, London, and São Paulo, during this project. Their meetings abroad were made easier because of the help and hospitality of Teija Katajainen of the WHO; Maria Alves of the EMA; Arthy Santhakumar of Chatham House; A. Srinivasa Chakravarthy, K.V. Surendra Nath,
and Syed Mohammed Arifullah of the U.S. Pharmacopeia–India; Carlos Morel of FIOCRUZ; and Laura Oliveira of the University of São Paulo. Charles Nwasor of the Altarum Institute, Kelley Badiane of USAID, Monica Eimunjeze of NAFDAC, Henrietta Williams of the Catholic Medical Association of Nigeria, and Isaac Umunna also helped the staff and committee prepare for their meetings.
The committee is grateful to the following participants who spoke at meetings and helped staff plan agendas:
Martin Harvey Allchurch
P.V. Appaji
Amir Attaran
Martin Auton
Sunil Bahl
Roger Bate
Ilisa Bernstein
Katherine Bond
Regina Brown
Gian Luca Burci
Claudio Henrique Cabral
Nicholas Cappuccino
Ranjan Chakrabarti
Ranjit Chaudhury
Lim Chin Chin
John Clark
Charles Clift
David Cockburn
Emer Cooke
Ediná Alves Costa
Alan Coukell
Elize Massard da Fonseca
Filipe Soares Quirino da Silva
Ashok Dang
Joelle Daviaud
Leandro Teixeira de Morais
Jenifer Devine
Pritu Dhalaria
Albinus D’Sa
Douglas Duarte
Paul Ellis
Frederico Benite Filho
Michele Forzley
Odile Frank
Laurie Garrett
David R. Gaugh
Debora Germano
Raj Shankar Ghosh
Ashifi Gogo
Antony Raj Gomes
Subhash Gouda
L.C. Goyal
Wendy Greenall
Jeffery Gren
Catherine Hill-Herndon
Meghana Inamdar
Mariaou Tala Jallow
Kees de Joncheere
Connie Jung
Mohga Kamal-Yanni
Harparkash Kaur
Sabine Kopp
Alan Leather
Jamie Love
Rohit Malpani
Paola Manchisini
Linda Marks
Sylvia Meek
Mayira Milano
Bejon Misra
Archna Mudgal
Koduru Surendra Nath
Paul Newton
Fernando Nogueira
Doroteia Koparanova Ollivier
Arun Panda
Sharon Peacock
Patrícia Oliveira Pereira
Rebeca Mancini Pereira
Greg Perry
Terezinha de Jesus Andreoli Pinto
Aline Plancon
Flávia Poppe
Tiago Lanius Rauber
Subbi Reddy
Christophe Rérat
Judit Rius
Nicolina Romano-Lieber
Francis Roodt
Luciano Gonçalves Rosado
Bruce Ross
Percy Alberto Ocampo Rujel
Niall Sargent
Philippa Saunders
Lynda Scammell
Aluísio Segurado
Nirupa Sen
Dilip Shah
Sangeeta Shashikant
Janice Soreth
Sadu Srivinas
Fergus Sweeny
Nirmalya Syam
Paulo Teixeira
Mary Lou Valdez
German Velasquez
Tarun Vij
Simeon Wilson
Mark Witkowski
Shunmay Yeung
Regina Zamith
Anthony Zook
Howard Zucker
ACTA |
Anti-Counterfeiting Trade Agreement |
ADDO |
Accredited Drug Dispensing Outlet |
AIDS |
acquired immune deficiency syndrome |
AMRH |
African Medicines Regulatory Harmonization |
Anvisa |
National Health Surveillance Agency of Brazil |
API |
active pharmaceutical ingredient |
BMI |
Business Monitor International |
CDC |
Centers for Disease Control and Prevention |
CHAI |
Clinton Health Access Initiative |
DFID |
Department for International Development |
DOTS |
Directly Observed Treatment–Short Course |
EMA |
European Medicines Agency |
ESI |
electrospray ionization |
EU |
European Union |
FDA |
U.S. Food and Drug Administration |
FIP |
International Pharmaceutical Federation |
GC-MS |
gas chromatography and mass spectrometer |
Global Fund |
Global Fund to Fight AIDS, Tuberculosis, and Malaria |
HIV |
human immunodeficiency virus |
HPLC |
high-performance liquid chromatography |
ICH |
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use |
IFC |
International Finance Corporation |
IMPACT |
International Medical Products Anti-Counterfeiting Taskforce |
Medicrime Convention |
Council of Europe Convention on the counterfeiting of medical products and similar crimes involving threats to public health |
MSF |
Médecins Sans Frontières (Doctors Without Borders) |
MSH |
Management Sciences for Health |
NABP |
National Association of Boards of Pharmacy |
NGO |
nongovernmental organization |
NIST |
National Institute of Standards and Technology |
NSF |
National Science Foundation |
OECD |
Organisation for Economic Co-operation and Development |
OPIC |
Overseas Private Investment Corporation |
PhRMA |
Pharmaceutical Research and Manufacturers of America |
PQM |
Promoting the Quality of Medicines |
PSI |
Pharmaceutical Security Institute |
PSM |
Partnership for Safe Medicines |
RFID |
radio frequency identification |
SBIR |
Small Business Innovation Research |
SSFFC |
substandard, spurious, falsely-labeled, falsified, counterfeit |
TLC |
thin layer chromatography |
TRIPS |
Trade-Related Aspects of Intellectual Property Rights |
Unicef |
United Nations Children’s Fund |
UNODC |
United Nations Office on Drugs and Crime |
USAID |
United States Agency for International Development |
USP |
U.S. Pharmacopeia |
Contents
Intellectual Property and Public Health
TRIPS and the Doha Declaration
Patent and Trademark Infringement
Competing Meanings of the Term Counterfeit
Substandard and Falsified Drugs
The Problem of Unregistered Medicines
Registration Agencies and National Pharmaceutical Authorities
Medications for Chronic Diseases
Medications for Infectious Diseases
Other Antiparasitic Resistance
Economic and Social Consequences
Social and Developmental Costs
3 THE MAGNITUDE OF THE PROBLEM
The Pharmaceutical Security Institute Incident Reporting System
Government and Intergovernmental Investigations
The FDA Office of Criminal Investigations
International Police Investigations
Case Reports and Convenience Samples
Systematic Random Samples of Drug Quality
The WHO Global Capacity-Building Project
4 CAUSES OF FALSIFIED AND SUBSTANDARD DRUGS
Procurement and Substandard Medicines
Applying the Model Quality Assurance System to Secondary Procurement
Corruption and Organized Crime
5 WEAKNESSES IN THE DRUG DISTRIBUTION CHAIN
An Overview of Drug Distribution in Developed and Developing Countries
The Wholesale Market in Low- and Middle-Income Countries
Drug Resale and Late Diversion
Tracking and Tracing Products Through the Supply Chain
Electronic Product Codes and Radio Frequency Identification
Unregistered Pharmacies in Low- and Middle-Income Countries
Shortage of Quality-Assured Drug Shops
Shortage of Trained Pharmacy Staff
Giving Incentives to Pharmaceutical Personnel
Internet Pharmacies in Middle- and High-Income Countries
The Legality of Internet Drugs Retail
The Attraction of Internet Pharmacies
Distinguishing Rogue Pharmacies from Legitimate Ones
Qualitative and Quantitative Methods
Overview of Detection, Screening, and Analytical Techniques
Visual Inspection and Package Technologies
Physical and Bulk Property Testing
FIGURES
TABLES
Medicines Use to Treat the Most Common Causes of Child Death Are Compromised in Developing Countries |
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