ADVANCING THE
DISCIPLINE OF
REGULATORY SCIENCE

FOR MEDICAL PRODUCT
DEVELOPMENT

An Update on Progress and
a Forward-Looking Agenda

Workshop Summary

Morgan L. Boname, Amanda Wagner Gee, and Anne B. Claiborne,
Rapporteurs

Forum on Drug Discovery, Development, and Translation

Board on Health Sciences Policy

Health and Medicine Division

THE NATIONAL ACADEMIES PRESS

Washington, DC

www.nap.edu

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by AbbVie, Inc.; the American Diabetes Association; American Society of Microbiology; Amgen Inc. (Contract No. GHCCOPS-CSARF-63987); Association of American Medical Colleges; AstraZeneca; Baxter BioScience; Burroughs Wellcome Fund (Contract No. 1015149); Critical Path Institute; Doris Duke Charitable Foundation (Contract No. 2015103); Eli Lilly & Co.; FasterCures; Friends of Cancer Research; GlaxoSmithKline (Contract No. 005319); Johnson & Johnson; Merck & Co., Inc. (Contract No. CMO-141224-000649); National Institutes of Health (NIH) (Contract No. HHSN263201200074I; Task Order HHSN26300023): National Cancer Institute (NIH), National Center for Advancing Translational Sciences (NIH), National Institute of Allergy and Infectious Diseases (NIH), National Institute of Mental Health (NIH), and National Institute of Neurological Disorders and Stroke (NIH); New England Journal of Medicine; Pfizer Inc.; Sanofi; Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Contract No. 1R13FD005496-01). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-43884-1
International Standard Book Number-10: 0-309-43884-5
Digital Object Identifier: 10.17226/23438

Additional copies of this report 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.

Copyright 2016 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Advancing the discipline of regulatory science for medical product development: An update on progress and a forward-looking agenda: Workshop summary. Washington, DC: The National Academies Press. doi: 10.17226/23438.

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Ralph J. Cicerone is president.

The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president.

The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.

The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.

Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national-academies.org.

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PLANNING COMMITTEE ON ADVANCING THE DISCIPLINE OF REGULATORY SCIENCE FOR MEDICAL PRODUCT DEVELOPMENT: AN UPDATE ON PROGRESS AND A FORWARD-LOOKING AGENDA¹

MARTIN PHILBERT (Co-Chair), University of Michigan School of Public Health, Ann Arbor, MI

ALASTAIR WOOD (Co-Chair), Symphony Capital, New York, NY

RUSS ALTMAN, Stanford University, CA

SHARON HESTERLEE, Myotonic Dystrophy Foundation, San Francisco, CA

RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC

EMMA MEAGHER, University of Pennsylvania, Philadelphia, PA

ROBERT MEYER, University of Virginia School of Medicine, Charlottesville, VA

STEPHEN OSTROFF, U.S. Food and Drug Administration, Silver Spring, MD

PAUL SELIGMAN, Amgen Inc., Thousand Oaks, CA

BRIAN STROM, Rutgers, the State University of New Jersey, Newark, NJ

HMD Staff

ANNE B. CLAIBORNE, Forum Director

CHRISTOPHER J. DEFEO, Program Officer

EMILY R. BUSTA, Associate Program Officer

KATHRYN M. HOWELL, Senior Program Assistant

ANDREW M. POPE, Director, Board on Health Sciences Policy

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s 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

RUSS ALTMAN (Co-Chair), Stanford University, CA

STEVEN 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

ANN BONHAM, Association of American Medical Colleges, Washington, DC

LINDA BRADY, National Institute of Mental Health, Bethesda, MD

GAIL CASSELL, Harvard Medical School Department of Social and Global Medicine (Visiting), Carmel, IN

ANDREW DAHLEM, Eli Lilly & Co., Indianapolis, IN

JAMES DOROSHOW, National Cancer Institute, Bethesda, MD

JEFFREY DRAZEN, New England Journal of Medicine, Boston, MA

JODIE GILLON, AstraZeneca, Summit, NJ

HARRY GREENBERG, Stanford University School of Medicine, CA (until December 31, 2015)

LYNN HUDSON, Critical Path Institute, Tucson, AZ

S. CLAIBORNE JOHNSTON, Dell Medical School, University of Texas, Austin

JACK KEENE, Duke University Medical Center, Durham, NC (until December 31, 2015)

RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC

KATE KNOBIL, GlaxoSmithKline, Collegeville, PA

RONALD KRALL, University of Pittsburgh, Steamboat Springs, CO (until December 31, 2015)

FREDA LEWIS-HALL, Pfizer Inc., New York, NY

BERNARD MUNOS, InnoThink Center for Research in Biomedical Innovation, Indianapolis, IN

ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation, New York, NY (until December 31, 2015)

JOHN ORLOFF, Baxalta, Deerfield, IL

ROBERT RATNER, American Diabetes Association, Alexandria, VA

MICHAEL ROSENBLATT, Merck & Co., Inc., Kenilworth, NJ

MICHAEL SEVERINO, AbbVie, Inc., North Chicago, IL

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s 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.

ELLEN SIGAL, Friends of Cancer Research, Washington, DC

LANA SKIRBOLL, Sanofi, Washington, DC

BRIAN STROM, Rutgers, the State University of New Jersey, Newark

JANET TOBIAS, Ikana Media, New York, NY (until December 31, 2015)

JOHN WAGNER, Takeda Pharmaceuticals, Cambridge, MA

JOANNE WALDSTREICHER, Johnson & Johnson, New Brunswick, NJ

CARRIE WOLINETZ, National Institutes of Health, Bethesda, MD

JANET WOODCOCK, U.S. Food and Drug Administration, Silver Spring, MD

HMD Staff

ANNE B. CLAIBORNE, Forum Director

CHRISTOPHER J. DEFEO, Program Officer (until October 2015)

REBECCA A. ENGLISH, Program Officer

AMANDA WAGNER GEE, Program Officer (as of November 2015)

EMILY R. BUSTA, Associate Program Officer (until December 2015)

MORGAN L. BONAME, Associate Program Officer (as of December 2015)

OLIVIA C. YOST, Senior Program Assistant (as of December 2015)

KATHRYN M. HOWELL, Senior Program Assistant (until November 2015)

ANDREW M. POPE, Director, Board on Health Sciences Policy

Reviewers

This workshop summary has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. 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:

Brian Alexander, Harvard Medical School

Jesse Goodman, Georgetown University

Peter Honig, Pfizer Inc.

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 Barry S. Coller, The Rockefeller University. He 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 AND ABBREVIATIONS

1 INTRODUCTION

Organization of This Report

2 CHARACTERIZING THE REGULATORY SCIENCE LANDSCAPE

Innovative Science at FDA

The Role of Data Science in Regulatory Science: A Case Study in Collaboration

3 REGULATORY SCIENCE APPLICATIONS: USING CASE STUDIES TO FOCUS ON APPROACHES TO ADVANCE THE DISCIPLINE

Identification and Development of Meaningful Biomarkers

Integrating Clinical Trial Data

Next-Generation Surveillance

Innovative Modeling for Integrating Data

4 REGULATORY SCIENCE INFRASTRUCTURE AND WORKFORCE

Characterizing the Discipline of Regulatory Science

Training the Next-Generation Regulatory Scientist

Incentivizing and Funding Regulatory Science

5 CHALLENGES AND OPPORTUNITIES IN REGULATORY SCIENCE

Regulatory Science Landscape Considerations

Considerations for Applications of Regulatory Science

Infrastructure and Workforce Considerations

APPENDIXES

A Bibliography

B Workshop Agenda

C Participant Biographies

Boxes and Figure

BOXES

1-1 Statement of Task

2-1 Key Examples of the Role of Data Science in Regulatory Science as Identified by the UCSF–Stanford CERSI Leadership

3-1 Basic Science of Measurement: Metrology for Principles of Biomarkers

3-2 Potential Concerns for Data Sharing

3-3 Update: FDA Sentinel

3-4 Selected Examples of Challenges and Limitations of Web-Based Surveillance

4-1 Examples of Regulatory Scientists as Multidisciplinary Communicators

4-2 Examples of Core Thematic Areas of Regulatory Science

FIGURE

3-1 Pathways to integrate biomarkers in drug development at U.S. FDA

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Acronyms and Abbreviations