Development of FDA regulated medical products a translational approach, second edition

Development of FDA-Regulated Medical Products Also available from ASQ Quality Press: Medical Device Design and Regulation Carl T DeMarco CAPA for the FDA-Regulated Industry José Rodríguez-Pérez The FDA and Worldwide Quality System Requirements Guidebook for Medical Devices, Second Edition Amiram Daniel and Ed Kimmelman The Certified HACCP Auditor Handbook ASQ Food, Drug, and Cosmetic Division Root Cause Analysis: Simplified Tools and Techniques, Second Edition Bjørn Andersen and Tom Fagerhaug HALT, HASS, and HASA Explained: Accelerated Reliability Techniques, Revised Edition Harry W McLean The Quality Improvement Handbook, Second Edition ASQ Quality Management Division; John E Bauer, Grace L Duffy, and Russell T Westcott, editors The Quality Toolbox, Second Edition Nancy R Tague Root Cause Analysis: The Core of Problem Solving and Corrective Action Duke Okes The Certified Quality Engineer Handbook, Third Edition Connie M Borror, editor To request a complimentary catalog of ASQ Quality Press publications, call 800-248-1946, or visit our website at www.asq.org/quality-press Development of FDA-Regulated Medical Products A Translational Approach Second Edition Elaine Whitmore ASQ Quality Press Milwaukee, Wisconsin American Society for Quality, Quality Press, Milwaukee 53203 © 2012 by ASQ All rights reserved Published 2012 Printed in the United States of America 18 17 16 15 14 13 12 Library of Congress Cataloging-in-Publication Data Whitmore, Elaine   Development of FDA-regulated medical products : a translational approach / Elaine   Whitmore.—2nd ed   p cm   Includes bibliographical references and index   ISBN 978-0-87389-833-1 (hard cover : alk paper)   Drug approval—United States.  Biological products—Standards—United States   Medical instruments and apparatus—Standards—United States.  United States   Food and Drug Administration.  I Title   RA401.5.W47 2012  615.1'9—dc23 2011051569 ISBN: 978-0-87389-833-1 No part of this book may be reproduced in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher Publisher: William A Tony Acquisitions Editor: Matt T Meinholz Project Editor: Paul Daniel O’Mara Production Administrator: Randall Benson ASQ Mission: The American Society for Quality advances individual, organizational, and community excellence worldwide through learning, quality improvement, and knowledge exchange Attention Bookstores, Wholesalers, Schools, and Corporations: ASQ Quality Press books, video, audio, and software are available at quantity discounts with bulk purchases for business, educational, or instructional use For information, please contact ASQ Quality Press at 800-248-1946, or write to ASQ Quality Press, P.O Box 3005, Milwaukee, WI 53201-3005 To place orders or to request ASQ membership information, call 800-248-1946 Visit our website at http://www.asq.org/quality-press   Printed on acid-free paper In loving memory of Emma and James Peters (This page intentionally left blank) Table of Contents List of Figures and Tables xi Acronyms and Abbreviations xv Preface xvii Part I  Unique Challenges in Medical Product Development Chapter 1  Pushing the Pipeline: Translational Research and Product Development Productivity Gap Translational R&D Valley of Death 11 Translational Research and FDA Initiatives 13 Driving Biomedical Innovation 14 Chapter 2  Healthcare in the United States 19 Chapter 3  It’s Not Your Father’s FDA: The “Modernization” of Medical Product Regulation 25 Food and Drug Administration Modernization Act of 1997 (FDAMA) 25 Prescription Drug User Fees 27 Information on Off-Label Use and Economics 28 Risk-Based Regulation of Medical Devices 28 Standards for Medical Products 29 The New FDA 29 Chapter 4  Classifying Medical Products 35 Drugs and Biologics 36 Drugs 37 vii viii   Table of Contents Biologics 38 FDA Consolidation of Drugs and Biologics 41 Medical Devices 43 Combination Products 46 Chapter 5  Product Liability and Product Development 53 Preemption 54 Medical Devices 54 Drugs 55 Basis of Product Liability 56 Design Defects 56 Warning Defects 57 Manufacturing Defects 57 The Role of Product Development Planning 57 Part II  Bringing a New Medical Product to Market Chapter 6  Overview of the Approval Processes for Drugs, Biologics, and Medical Devices 63 Drugs 64 Screening 64 Preclinical Testing 64 Investigational New Drug Application 65 Clinical Trials 65 New Drug Application 66 Inspections 66 Generic Drugs and Abbreviated New Drug Applications 67 Biologics 68 Biosimilar Products (Follow-On Biologics) 68 Medical Devices 69 General Controls 71 Special Controls 72 Premarket Notification 73 Premarket Approval 75 Chapter 7  Quality by Design 77 Design Controls 78 Design and Development Planning 81 Design Input 83 Design Output 83 Design Review 84 Table of Contents   ix Design Verification and Validation 84 Design Transfer 85 Design Changes 85 Design History File (DHF) 85 Other Considerations in Design Controls 85 Chapter 8  Designing-Out Disaster: Risk Analysis 87 Quality Risk Management 90 Risk Analysis Techniques 91 Chapter 9  Recalls, Withdrawals, ­and Revocations 95 Recalls 95 Firm-Initiated Recalls 96 FDA-Requested Recalls 96 FDA-Ordered Recalls 96 Withdrawals 97 Revocations 97 Influence of Product Development Planning 100 Chapter 10  Human Factors and Usability Engineering: Minimizing Medical Errors 103 Chapter 11  Is It Safe and Does It Work? Evaluating Safety and Efficacy in Clinical Trials 115 Preclinical Testing 116 Clinical Trials 120 Drugs and Biologics 122 Endpoints and Biomarkers 123 Medical Devices 124 Diversity in Clinical Trials 127 Chapter 12  How Much Is the Product Really Worth? Outcomes Research, Pharmacoeconomics, and Managed Care 129 Clinical Outcomes 131 Pharmacoeconomics and Economic Outcomes 131 Quality-of-Life Outcomes 131 Comparative Effectiveness Research 133 Outcomes and Product Development Planning 134 Part III  Product Development Planning Chapter 13  Models and Metaphors: Product Development and the Product Development Organization 139 Swimming Against the Stream 140 x   Table of Contents The Cross-Functional Organization 141 Chapter 14  Components of Product Development Planning: The Product Development Process 149 Stage 1—Discovery 152 Stage 2—Feasibility 156 Stage 3—Optimization 158 Stage 4—Demonstration 159 Stage 5—Production 159 Stage 6—Launch and Follow-Through 160 Chapter 15  Components of Product Development Planning: Development Portfoliio Management 161 Killing a Project 172 Chapter 16  Components of Product Development Planning: Technology Assessment 175 Chapter 17  Components of Product Development Planning: Technology Forecasting 183 Chapter 18  Better Double-Check That: A Guide for the Risk-Averse 193 Planning for Promotional Opportunities 193 Speed to Market versus Product Promotional Preferences 195 Intellectual Property 195 Don’t Forget the Budget 198 Conflict Resolution: What About Game Theory? 199 Decision-Making Games 200 Global Games 201 Product Development Ecosystem Games 201 Quality Challenges 202 Chapter 19  Where Do We Go From Here? 207 In Closing 208 Appendix: Resources 211 Endnotes 219 Glossary 225 Index 231 ... website at www.asq.org/quality-press Development of FDA- Regulated Medical Products A Translational Approach Second Edition Elaine Whitmore ASQ Quality Press Milwaukee, Wisconsin American Society... the obstacles calls for a revision in attitudes and processes related to medical product development Enter translational research Translational research—also frequently called translational science... potentially important treatments and cures are lost The NIH has taken a lead role in drawing attention to the preclinical valley of death and to the objectives of translational research The agency also