The New Medicines: How Drugs are Created, Approved, Marketed, and Sold PDF
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BERNICE SCHACTER THE NEW MEDICINES How Drugs Are Created, Approved, Marketed, and Sold PRAGER Westport, Connecticut London Library of Congress Cataloging-in-Publication Data Schacter, Bernice Zeldin, 1943- The new medicines : how drugs are created, approved, marketed, and sold / Bernice Schacter. p. cm. Includes bibliographical references and index. ISBN 0-275-98141-X (alk. paper) 1. Drug development—Popular works. 2. Clinical trials—Popular works. 3. Pharmaceutical industry—Popular works. 4. Consumer education. I. Title. [DNLM: 1. Drug Industry—organization & administration—United States. 2. Pharmaceutical Preparations—economics—United States. 3. Clinical Trials—United States. 4. Drug Design—United States. 5. Drugs, Investigational—economics—United States. 6. Legislation, Drug—United States. QV 736 S291n 2006] RM301.25.S34 2006 615U9—dc22 2005019187 British Library Cataloguing in Publication Data is available. Copyright © 2006 by Bernice Schacter All rights reserved. No portion of this book may be reproduced, by any process or technique, without the express written consent of the publisher. Library of Congress Catalog Card Number: 2005019187 ISBN: 0-275-98141-X First published in 2006 Praeger Publishers, 88 Post Road West, Westport, CT 06881 An imprint of Greenwood Publishing Group, Inc. www.praeger.com Printed in the United States of America The paper used in this book complies with the Permanent Paper Standard issued by the National Information Standards Organization (Z39.48-1984). 10 987654321 Contents Preface v Abbreviations and Acronyms ix 1 The Path from Bench to Bedside 1 2 How Did the FDA Get to Be in Charge? The History of Regulation of Human Drugs 13 3 The Eureka Moment: How New Medicines Are Discovered 21 4 Test Tube Results Are Not Enough: Animal Tests for a Drug's Utility 37 5 The Business Decisions: Committing to Development 47 6 Production of the New Drug 57 7 Laboratory and Animal Safety Testing 65 8 Getting Set for Clinical Trials 81 9 Phase 1 Clinical Trials 93 10 Phase 2 Clinical Testing 101 iv Contents 11 Phase 3 Testing 113 12 Putting Together the Application for Approval: The New Drug Application (NDA) 123 13 Everybody Holds Their Breath: Will the FDA File the NDA? 135 14 The FDA Review 143 15 What Do Outside Experts Think? The Advisory Committee Meeting and FDA Approval 161 16 The Launch: Marketing the Drug 181 17 It's Not Over Till It's Over: Post-Approval Studies 201 18 Are We (Well) Served? Do We Have the System, Industry, and Regulations We Need, Want, and Deserve? 223 Bibliography 237 Index 259 Preface Do we have the pharmaceutical industry we need and want? Perhaps not, but it is the industry that our innova tive and entrepreneurial society and responsive regulatory system has given us. And knowing how it works may allow us to make better decisions as patients, caregivers, and citizens. The seed for this book began in 1984 when, with little forethought, I landed in the midst of an industrial effort, the fruits of which had benefited me but the workings of which were pretty much unknown to me. After serving in an academic position where I did research, taught immunology to medical students, and ran a laboratory that matched people for organ transplants, I moved to a research scientist position at what was then Bristol-Myers, where I was quickly ex posed to the steps of drug discovery and development. With no wall separating the research and development work, department and divi sion review meetings provided ample opportunities for a glimpse of what it took to morph an idea into a drug in a bottle. It did not hurt that my spouse was immersed in the same process on the clinical side. "Phases," "the Agency," and "project status" became my jargon, VI Preface though my nominal assignment was as a lab jock and I worked hard at it. It also did not hurt that through my academic experience and by propinquity (i.e., marriage) I had learned a little bit of clinical medicine (always a dangerous thing) or that Bristol licensed a puta tive anticancer drug that I thought demanded my championing for selection for development as a drug for organ transplantation pa tients. I am nosy and always want to know about everyone's job. People like talking about what they do, and even if they grouse, a lit tle sympathy and a few questions will get them explaining over a cup of coffee. After seven years, the maelstrom of a corporate merger (with Squibb), two years leading R&D at a biotech start-up, and a chronic illness that precluded the career fast track, I was back in the class room, eventually teaching science to nonscientists. What better ped agogic platform than "How did that pill get into the bottle?" More homework (lots of homework—bless the Internet and online libraries), and I had a course. Then a book seemed a nifty way to pull the curtain back for a larger audience and expose the wizard that puts the pills in the bottle. Current posturing by the usual and always righteous suspects notwithstanding, the wizard is neither inherently evil nor unusually fumbling. The wizard is no saint either. Getting the pill in the bottle and into your medicine cabinet and mine takes the dedi cated, clear-eyed efforts of scores of smart, generally conscientious, and often very ambitious people who are as fallible as any such group. I think the story of their efforts and fumbles is worth know ing because as citizens, investors, and, yes, as patients, we have to make judgments about how well they do their jobs of moving the drug bit by bit along its proscribed and treacherous path. I must acknowledge the help and counsel of many (now former) Bristol-Myers people for my education, particularly, but in no partic ular order: Stephen Carter, Sal Forenza, Al Crosswell, Sue Hubencz, Cheryl Anderson, Robert Wittes, Terry Doyle, Anna Casazza, Bill Rose, John Shurig, George Spitalny, Joe Brown, Alice Leung, and so many others who either patiently explained some nuance of their part of the process or, in the case of my supervisors, expected that I would learn all this to better do my job. Preface VII In developing this book, I shamelessly called on the expertise and patience of Kevin O'Neill, Jerry Merritt, Frank Bamborolla, Susan Anderson, Donna Francher, and Lottie Wang. I am also deeply in debted to John Talley, Stuart Scheindlin, and Irit Pinchasi not only for their patience but also for their willingness and ability to recall events in the distant past. Thanks, too, to Kevin Downing for his wise coun sel and skillful editing. Beyond all, I must give profound thanks to my husband, Lee P. Schacter, Ph.D., M.D., for creating the opportunity to enter this world and for sharing his education in drug development with me. We "talk" science endlessly, as our patient daughters can attest, and share the professional challenges we face. Lee is smart, wise, knowl edgeable, and ethical, a combination hard to match. He taught me that the ethics of medical research not only allow rigorous science but also require it. For that I give my humble and loving thanks. As for his patience when I am writing, I can only ask, again, "It wasn't so bad, was it?" So, too, I ask Beth and Sara. This page intentionally left blank Abbreviations and Acronyms AD Alzheimer's Disease ADME Absorption, Distribution, Metabolism, and Elimination ALL Acute Lymphoblastic Leukemia AMP Average Manufacturer Price ANDA Abbreviated New Drug Application AUC Area Under the Curve AWA Animal Welfare Act BLA Biological License Application CBER Center for Biologies Evaluation and Research CDC Centers for Disease Control CDER Center for Drug Evaluation and Research CFR Code of Federal Regulations CGCP Current Good Clinical Practice CGLP Current Good Laboratory Practice CGMP Current Good Manufacturing Practice COX Cyclooxygenase CRF Case Report Form
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