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MEDICAL DEVICES
AND THE
PUBLIC’S HEALTH
THE FDA 510(k) CLEARANCE PROCESS AT 35 YEARS
Committee on the Public Health Effectiveness of the
FDA 510(k) Clearance Process
Board on Population Health and Public Health Practice
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Govern-
ing 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. HHSF223200810020I, Task Order #13
between the National Academy of Sciences and the Department of Health and Hu-
man Services. 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: 978-0-309-21242-7
International Standard Book Number-10: 0-309-21242-1
Additional copies of this report are available from the National Academies Press,
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Copyright 2011 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). 2011. Medical Devices and the
Public’s Health: The FDA 510(k) Clearance Process at 35 Years. 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 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 en-
gineers. 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 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
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 Sci-
ences 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.
www.national-academies.org
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COMMITTEE ON THE PUBLIC HEALTH EFFECTIVENESS
OF THE FDA 510(k) CLEARANCE PROCESS
DAVID R. CHALLONER (Chair), Vice President for Health Affairs,
Emeritus, University of Florida, Gainesville, FL
GARY S. DORFMAN, Professor and Vice Chair for Research,
Department of Diagnostic Radiology, Weill Cornell Medical College,
New York, NY
BARBARA EVANS, Associate Professor; Codirector, Health Law
& Policy Institute; Director, Center on Biotechnology and Law,
University of Houston Law Center, Houston, TX
LAZAR J. GREENFIELD, Professor of Surgery and Chair Emeritus,
University of Michigan, Ann Arbor, MI
STEVEN GUTMAN, Associate Director, Technology Evaluation Center,
BlueCross BlueShield Association, Alexandria, VA
YUSUF M. KHAN, Assistant Professor, University of Connecticut Health
Center, Farmington, CT
DAVID KORN, Vice Provost for Research, Harvard University,
Boston, MA
ELIZABETH W. PAXTON, Director of Surgical Outcomes and Analysis,
Kaiser Permanente, San Diego, CA
SHARI LAWRENCE PFLEEGER, Director of Research, Institute for
Information Infrastructure Protection, Washington, DC
WILLIAM W. VODRA, Senior Counsel (Retired), Arnold & Porter, LLP,
Washington, DC
BRIAN WOLFMAN, Visiting Professor of Law, Georgetown University
Law Center, Washington, DC
KATHRYN C. ZOON, Scientific Director and Director, Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD
Consultant to the Committee
SUSANNE LUDGATE, Clinical Director, Medicines and Healthcare
Products Regulatory Agency, UK
Study Staff
ABIGAIL E. MITCHELL, Study Director
HEATHER M. COLVIN, Program Officer
MELISSA G. FRENCH, Associate Program Officer
KATHLEEN M. SHEPHERD, Senior Program Assistant
NORMAN GROSSBLATT, Senior Editor
ROSE MARIE MARTINEZ, Director, Board on Population Health and
Public Health Practice
v
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Reviewers
T
his report has been reviewed in draft form by persons chosen for their
diverse perspectives and technical expertise, in accordance with pro-
cedures 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
individual’s for their review of this report:
Halyna Breslawec, Cosmetic Ingredient Review
Paul Citron, Medtronic, Inc. (retired)
Khaled El Emam, University of Ottawa
Ellen Flannery, Covington & Burling, LLP
Thomas Fogarty, Fogarty Engineering
Gordon Gillerman, National Institute of Standards and Technology
George Isham, HealthPartners, Inc.
Alan Kent, Global Harmonization Task Force
Arthur Levin, Center for Medical Consumers
Mark B. McClellan, The Brookings Institution
Richard Merrill, University of Virginia
Richard Platt, Harvard Medical School
Miriam Provost, Biologics Consulting Group, Inc.
Fran Visco, National Breast Cancer Coalition
vii
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viii REVIEWERS
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 the report was overseen by Edwin P. Przybylowicz,
Eastman Kodak (retired) and Brian L. Strom, University of Pennsylvania
School of Medicine. Appointed by the National Research Council and In-
stitute of Medicine, respectively, they were responsible for making certain
that an independent examination of the report was carried out in accordance
with institutional procedures and that all review comments were carefully
considered. Responsibility for the final content of the report rests entirely
with the author committee and the institution.
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Acknowledgments
T
he committee thanks everyone who presented and participated in
panel discussions during the public workshops, informing our task
and assisting in developing our approach and thought process on
the statement task. The following individuals presented information at
the workshops: David Feigal, Arizona State University School of Law;
Robert Fischell, Neuralieve, Inc.; Kevin Fu, Department of Computer Sci-
ence, University of Massachusetts, Amherst; Susan Gardner, Center for
Devices and Radiological Health (CDRH), US Food and Drug Adminis-
tration (FDA); Ralph Hall, University of Minnesota Law School; Peter
Barton Hutt, Covington and Burling, LLP; David Jeffrys, Eisai Europe
Ltd.; William Maisel, formerly with the Medical Device Safety Institute
(now with the FDA); Josh Makower, ExploraMed Development, LLC;
Frederick Masoudi, Denver Health Medical Center; Eric Peterson, Divi-
sion of Cardiology, Duke University Medical Center; Philip Phillips, PCS,
LLC; Rita Redberg, Division of Cardiology, University of California, San
Francisco; Frederic Resnic, Brigham and Women’s Hospital; Janet Trunzo,
AdvaMed; Timothy Ulatowski, CDRH; and Paul Varosy, Department of
Veterans Affairs (VA) Eastern Colorado Health Care System. Doug Mowen,
of PricewaterhouseCoopers, was unexpectedly unable to present at the June
2010 workshop but provided materials for the committee’s review. Many
of the presenters also participated in the panel discussions. Other panel
discussants whom the committee thanks are Amy Allina, National Women’s
Health whom; Susan Alpert, Medtronic, Inc.; D. Bruce Burlington, indepen-
dent consultant; Larry Kessler, University of Washington School of Public
Health; and William Vaughan, consultant to Consumer’s Union.
ix
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x ACKNOWLEDGMENTS
The committee thanks the representatives of the FDA who provided
helpful information on CDRH, medical-device regulation, and various as-
pects of the 510(k) clearance process: Philip Desjardins, Maggie Dietrich,
Ann Ferriter, Christy Foreman, Heather Rosecrans, Donna-Bea Tillman,
and Jeffrey Shuren.
The committee thanks the authors of the commissioned papers: David
Feigal, Arizona State University School of Law; Kevin Fu, Department of
Computer Science, University of Massachusetts, Amherst; Larry Kessler,
University of Washington School of Public Health; William Maisel, Medical
Device Safety Institute; and Philip Phillips, PCS, LLC. The papers were an
excellent resource of information and proved to be very helpful. All affilia-
tions were contemporaneous.
The committee thanks members of the public who provided oral com-
ments during the public meetings and persons and organizations that sub-
mitted written materials and comments. There was a wide variety of points
of view in the commentary, and those viewpoints afforded valuable insight
into the complexity of the process and its outcomes. The time and effort
made in traveling to the public meetings and in preparing written materials
and statements were greatly appreciated.
The committee also thanks Katharine Larson and Lindsay S. Narvaez,
students at the University of Houston Law Center, for their assistance in
researching and formatting legal citations.
The committee thanks those who provided a critical perspective of the
European system of device regulation: Susanne Ludgate, of the Medicines
and Healthcare Products Regulatory Agency (UK), served as a consultant to
the committee, and Christopher Hodges, of the University of Oxford, also
provided extremely valuable insight into the European Union’s medical-
device regulatory system.
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Preface
T
he vast majority of the medical devices used in health care in the
United States that are reviewed by the US Food and Drug Admin-
istration (FDA) before entering the marketplace are cleared (not
approved) for human use in a process called premarket notification, or the
510(k) clearance process, named after Section 510(k) of the authorizing
legislation passed by Congress in 1976. Stimulated by reports of problems
with several 510(k)-cleared devices, the public, legislators, the Government
Accountability Office, the Department of Health and Human Services Of-
fice of the Inspector General, and the courts, including the Supreme Court,
have all questioned the logic and value of the 510(k) clearance process be-
ing used by a federal agency charged with responsibility for protecting and
promoting the public’s health. After 35 years, at a time of rapidly changing
science and technology, questions persist about whether the 510(k) process
is protecting and promoting the public’s health. Thus, the FDA asked the
Institute of Medicine (IOM) to evaluate the 510(k) clearance process and to
make recommendations aimed at protecting the health of the public while
preserving the legitimate interests of industry and patients by making avail-
able a mechanism to achieve timely access of medical devices to the market.
The committee determined that it could not evaluate the 510(k) clear-
ance process for bringing devices to market in isolation; it was necessary to
understand the full spectrum of devices reviewed by the FDA—from the sim-
plest tongue depressor to the most complex implantable devices. The 510(k)
clearance process, the mechanism used for premarket review of most Class
II devices, is embedded in the vast middle. In reviewing the legislative and
regulatory history of the 510(k) program, the committee found that it was
designed in 1976 to provide only a determination of the substantial equiva-
xi
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xii PREFACE
lence of a new device to an already marketed (predicate) device; it was not
designed to determine whether a new device provides a reasonable assurance
of safety and effectiveness or whether it promotes innovation. That finding
complicated the committee’s work in that the FDA, in the charge to the com-
mittee, stated that the goals of the 510(k) clearance process are to “make
available to consumers devices that are safe and effective” and to “promote
innovation in the medical device industry.” The committee struggled with how
to address the conflict between the legislative framework of the program and
the FDA’s stated goals.
The report lays out the committee’s rationale and approach for address-
ing this conflict and provides recommendations to the FDA that it believes
will result in an improved regulatory system for bringing Class II medical
devices to market. The recommendations are focused on strengthening the
science base needed to make better-informed regulatory decisions and on
giving the FDA the tools that it needs to identify and remove problematic de-
vices from the market. The committee believes that taking the recommended
steps will generate the information needed to design a robust regulatory
framework for Class II devices. The new framework would increase the
public’s confidence that safe and effective medical devices are being made
available in a timely manner.
Because of the high visibility of concerns about the 510(k) clearance
process, the FDA has undertaken its own internal study in parallel with
the IOM study to determine how the process might be improved within the
FDA’s existing legislative authorities. Although IOM was not specifically
charged with weighing in on or critiquing the FDA’s recommendations, the
committee did use the FDA’s data and analyses in reaching its own conclu-
sions and recommendations.
I would like to thank the members of the committee for their incred-
ibly hard work over the past 16 months. They came from very different
backgrounds and perspectives on the development and use of devices for
human health care. The time that the committee members invested in this
study was considerable. Although their discussions and deliberations often
were spirited, they collaborated effectively and reached consensus on the
findings, conclusions, and recommendations.
Finally, the committee thanks the IOM staff, including the study direc-
tor, Abigail Mitchell; the program officer, Heather Colvin; the associate
program officer, Melissa French; and the senior program assistant, Kathleen
Shepherd. The staff’s efforts were essential in the information-gathering and
writing process, and in providing the committee with necessary assistance
and support.
David R. Challoner, Chair
Committee on the Public Health Effectiveness of the
FDA 510(k) Clearance Process
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Contents
ACRONYMS AND ABBREVIATIONS xix
SUMMARY 1
The Committee’s Task, 4
Conclusions, 4
Recommendations, 7
1 INTRODUCTION 15
What Is a Medical Device?, 16
The Challenge of Regulating Medical Devices, 17
The Committee’s Approach to Its Task, 19
Attributes of an Ideal Medical-Device Regulatory System, 21
Center for Devices and Radiological Health Activities
Related to the 510(k) Process, 22
Organization of the Report, 26
References, 26
2 KEY MEDICAL-DEVICE LEGISLATIVE AND REGULATORY
ACTIONS 29
The 1938 Act, 30
The 1976 Act, 30
The 1990 Act, 34
The 1997 Act, 37
The 2002 and 2007 Acts, 38
Summary of Findings, 39
References, 40
xiii
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xiv CONTENTS
3 COMPONENTS OF US MEDICAL-DEVICE REGULATION 41
Tools and Authorities for Regulating Marketed Devices, 41
Food and Drug Administration Enforcement and Other Powers, 54
Comparison of the Food and Drug Administration’s Authorities
Over Marketed Drugs and Marketed Devices, 62
Device Classification and Premarket Review, 68
Infrastructure of the Center for Devices and Radiological Health, 73
Summary of Findings, 82
References, 82
4 THE 510(k) CLEARANCE PROCESS 85
Implementation of the 510(k) Process, 86
Evidence Supporting 510(k) Submissions, 104
De Novo Premarket Review, 115
Summary of Findings, 118
References, 119
5 POSTMARKETING SURVEILLANCE, COMPLIANCE, AND
ENFORCEMENT 123
The Food and Drug Administration’s Current Postmarketing
Surveillance Activities, 124
Non–Food and Drug Administration Postmarket Data-Collection
Efforts, 137
Communicating with Consumers, 142
Summary of Findings, 143
References, 144
6 EXTERNAL FACTORS THAT AFFECT THE MEDICAL-DEVICE
REGULATORY SYSTEM 149
The Growing Number and Complexity of Medical Devices, 149
Innovation and the 510(k) Clearance Process, 164
The Medical-Device Ecosystem, 169
Globalization of the Medical-Device Industry, 173
Summary of Findings, 184
References, 185
7 CONCLUSIONS AND RECOMMENDATIONS 189
Protecting the Public’s Health by Ensuring the Safety and
Effectiveness of Medical Devices, 190
Facilitating Innovation in Support of Public Health, 193
Recommendations, 196
References, 204
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xv
CONTENTS
APPENDIXES
A HISTORY OF MEDICAL-DEVICE LEGISLATION AND
REGULATION IN THE UNITED STATES 207
Device Regulation Under the 1938 Federal Food, Drug, and
Cosmetic Act, 211
Development and Enactment of the Medical Device
Amendments of 1976, 213
Basic Structure of the Medical Device Amendments, 214
Implementation of the Medical Device Amendments:
Long-Term Trends, 224
The Safe Medical Devices Act of 1990, 249
Developments in 1990–1997, 259
The Food and Drug Administration Modernization Act of 1997, 265
1997–2009 Developments, 272
Closing Observations, 275
References, 276
B COMMITTEE BIOGRAPHIES 279
INDEX 287
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Boxes, Figures, and Tables
BOXES
S-1 The Three Device Classes, 2
S-2 Definition of Substantial Equivalence in the 1990 Safe Medical
Devices Act, 3
1-1 Attributes of an Ideal Medical-Device Regulatory System, 21
1-2 CDRH’s Preliminary Finding and Recommendations from Its
Review of the 510(k) Clearance Process, 24
4-1 Case Study: Biliary Stents in Peripheral Vasculature, 99
5-1 Case Study: Cardiovascular Intravascular Filters, 136
6-1 Example Recall Announcement, 158
FIGURES
3-1 Federal government, Department of Health and Human Services,
and FDA funding, FY 2008, 74
3-2 Third-party 510(k) submissions as percentage of total 510(k)
submissions received, FY 1999–2009, 77
4-1 The FDA substantial-equivalence decision tree, 93
4-2 Percentage of 510(k) decisions within 90 FDA days,
FY 2002–2008, 111
xvii
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xviii BOXES, FIGURES, AND TABLES
4-3 Number of 510(k) review cycles, FY 2002–2008, 112
4-4 Number of de novo requests received, CY 1998–2009, 117
4-5 Average total time from 510(k) receipt to de novo approval, CY
2005–2009, 118
6-1 Original 510(k) submissions to CDRH, FY 1976–2009, 150
6-2 Number of 510(k) product codes, 1990–2009, 151
6-3 Pages per 510(k) submission and total page volume received, 1983–
2008, 152
6-4 Example of a medical-device software malfunction, 157
6-5 Transmission of medical data, 161
6-6 Vision of future data transmission, 162
TABLES
3-1 Comparison of FDA Authorities to Obtain Postmarket Information
on Risks Posed by Drugs and Medical Devices, 64
3-2 Comparison of FDA Authorities to Take Remedial Actions in Light
of New Safety Findings, 66
3-3 Summary of Key Differences Between PMA Applications and
510(k) Submissions, 72
3-4 Frequency of Problems with Third-Party Reviews of 510(k)
Submissions, 78
4-1 FDA Review Time by Availability of Guidance, 106
5-1 Medical-Device Adverse-Event Reports, 2003–2007, 125
6-1 European Commission Risk Classification Scheme, 179
6-2 Conformity Assessment Procedure by Class, 181
A-1 510(k) Submissions and Those Found Not Substantially Equivalent,
1976–1982, 231
A-2 510(k) Submissions and Those Found Not Substantially Equivalent,
FY 1989–1996, 232
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Acronyms and Abbreviations
AIMDD active implantable medical devices
ALJ administrative law judge
CA competent authority
CART Clinical Assessment, Reporting, and Tracking program
CBER Center for Biologics Evaluation and Research
CDER Center for Drug Evaluation and Research
CDRH Center for Devices and Radiological Health
CEN European Committee for Standardization
CFR Code of Federal Regulations
CMS Centers for Medicare and Medicaid Services
DEN Device Experience Network
DELTA Data Extraction and Longitudinal Time Analysis
DHR device history record
EHR electronic health record
EU European Union
FDA Food and Drug Administration
FDAAA Food and Drug Administration Amendments Act
FDAMA Food and Drug Administration Modernization Act
FFDCA Federal Food, Drug, and Cosmetic Act
FTC Federal Trade Commission
FTE full-time equivalent
xix
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xx ABBREVIATIONS
FY fiscal year
GAO Government Accountability Office (formerly General
Accounting Office)
GHTF Global Harmonization Task Force
GMP good manufacturing practices
HHS Department of Health and Human Services (formerly
Department of Health, Education, and Welfare)
HIMA Health Industry Manufacturers Association
IG inspector general
IOM Institute of Medicine
IVDD in vitro diagnostic medical devices
MAUDE Manufacturer and User Device Experience database
MD EPINET Medical Device Epidemiology Network
MDA Medical Device Amendments
MDR medical-device report
MedSun Medical Product Surveillance Network
NB notified body
NCDR ICD National Cardiovascular Data Registry for implantable
cardioverter defibrillators
NDA new drug application
NSE not substantially equivalent
OC Office of Compliance
OCP Office of Combination Products
ODE Office of Device Evaluation
OMB White House Office of Management and Budget
ORA Office of Regulatory Affairs
OTS off-the-shelf
PMA premarket approval
QSR quality-system regulations
SE substantially equivalent
SMDA Safe Medical Devices Act
STED summary technical document
UDI unique device identification
