The New Medicines: How Drugs are Created, Approved, Marketed, and Sold

281 Pages·2005·13.23 MB·English

by  Bernice Z. Schacter

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.
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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