Development of FDA-Regulated Medical Products

Elaine Whitmore

Description

Translating promising discoveries and innovations into useful, marketable medical products demands a robust process to guide nascent products through a tangle of scientific, clinical, regulatory, economic, social, and legal challenges. There are so many human and environmental elements involved in shepherding medical advances from lab to launch that the field of medical product development has been referred to as an ecosystem.
The purpose of this book is to help provide a shared foundation from which cross-functional participants in that ecosystem can negotiate the product development labyrinth and accomplish the goal of providing both groundbreaking and iterative new medical products. The book is intended for anyone in industry, the public sector, or academia—regardless of functional specialty, workplace, or seniority—who is interested in medical product development.
The years since the publication of the previous edition of this book have seen profound changes in the actions and attitudes of patients, insurers, manufacturers, and the Food and Drug Administration regarding the streamlining of medical product development and approval. What those years have not seen is a concomitant increase in innovative treatments with profound benefits to patients. Despite enormous investments in research by both private and public sources and a surge in scientific and technological advances, new medical products barely trickle into the marketplace. For a variety of reasons, applied sciences necessary for medical product development are not keeping pace with the tremendous advances in basic sciences.
Not surprisingly, industry and academia are under substantial pressure to transform discoveries and innovations from the laboratory into safe and effective medical products to benefit patients and improve health. This evolution—from bench to bedside—has become known as translational research and development, and this approach is what this book illuminates.
"I have been working in medical device design and design assurance for over 10 years…Elaine Whitmore really gets this right...The point is that quality regulations are not going to go away, and those responsible for healthcare product development will have to lead the charge to keep up the momentum in their organizations. I am going to have to buy several copies of this for my clients!" Joseph P. Sener, P.E.

Sujets

• Business
• Qualité, hygiène, sécurité, environnement
• Medical
• Médecine
• Biotechnology

Informations

• Publié par: ASQ Quality Press
• Date de parution: 15 février 2012
• Nombre de lectures: 0
• EAN13: 9780873892216
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Development of FDA-Regulated Medical Products
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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
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)
1. Drug approval—United States. 2. Biological products—Standards—United States. 3. Medical instruments and apparatus—Standards—United States. 4. 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.
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To place orders or to request ASQ membership information, call 800-248-1946. Visit our website at http://www.asq.org/quality-press .
In loving memory of Emma and James Peters.
Table of Contents
Development of FDA-Regulated Medical Products
List of Figures and Tables
Acronyms and Abbreviations
Preface
Part I: Unique Challenges in Medical Product Development
Chapter 1: Pushing the Pipeline
Productivity Gap
Translational R&D
Valley of Death
Translational Research and FDA Initiatives
Driving Biomedical Innovation
Chapter 2: Healthcare in the United States
Chapter 3: It’s Not Your Father’s FDA
Food and Drug Administration Modernization Act of 1997 (FDAMA)
Prescription Drug User Fees
Information on Off-Label Use and Economics
Risk-Based Regulation of Medical Devices
Standards for Medical Products
The New FDA
Chapter 4: Classifying Medical Products
Drugs and Biologics
Drugs
Biologics
FDA Consolidation of Drugs and Biologics
Medical Devices
Combination Products
Chapter 5: Product Liability and Product Development
Preemption
Medical Devices
Drugs
Basis of Product Liability
Design Defects
Warning Defects
Manufacturing Defects
The Role of Product Development Planning
Part II: Bringing a New Medical Product to Market
Chapter 6: Overview of the Approval Processes for Drugs, Biologics, and Medical Devices
Drugs
Screening
Preclinical Testing
Investigational New Drug Application
Clinical Trials
New Drug Application
Inspections
Generic Drugs and Abbreviated New Drug Applications
Biologics
Biosimilar Products (Follow-On Biologics)
Medical Devices
General Controls
Special Controls
Premarket Notification
Premarket Approval
Chapter 7: Quality by Design
Design Controls
Design and Development Planning
Design Input
Design Output
Design Review
Design Verification and Validation
Design Transfer
Design Changes
Design History File (DHF)
Other Considerations in Design Controls
Chapter 8: Designing-Out Disaster: Risk Analysis
Quality Risk Management
Risk Analysis Techniques
Chapter 9: Recalls, Withdrawals, and Revocations
Recalls
Firm-Initiated Recalls
FDA-Requested Recalls
FDA-Ordered Recalls
Withdrawals
Revocations
Influence of Product Development Planning
Chapter 10: Human Factors and Usability Engineering
Chapter 11: Is It Safe and Does It Work?
Preclinical Testing
Clinical Trials
Drugs and Biologics
Endpoints and Biomarkers
Medical Devices
Diversity in Clinical Trials
Chapter 12: How Much Is the Product Really Worth?
Clinical Outcomes
Pharmacoeconomics and Economic Outcomes
Quality-of-Life Outcomes
Comparative Effectiveness Research
Outcomes and Product Development Planning
Part III: Product Development Planning
Chapter 13: Models and Metaphors
Swimming Against the Stream
The Cross-Functional Organization
Chapter 14: Components of Product Development Planning
Stage 1—Discovery
Stage 2—Feasibility
Stage 3—Optimization
Stage 4—Demonstration
Stage 5—Production
Stage 6—Launch and Follow-Through
Chapter 15: Components of Product Development Planning
Killing a Project
Chapter 16: Components of Product Development Planning
Chapter 17: Components of Product Development Planning
Chapter 18: Better Double-Check That
Planning for Promotional Opportunities
Speed to Market versus Product Promotional Preferences
Intellectual Property
Don’t Forget the Budget
Conflict Resolution: What About Game Theory?
Decision-Making Games
Global Games
Product Development Ecosystem Games
Quality Challenges
Chapter 19: Where Do We Go From Here?
In Closing
Appendix: Resources
Organizations
Government Health Statistics
Regulations
Food and Drug Administration
Endnotes
Glossary
List of Figures and Tables
Figure 1.1 Pharmaceutical industry R&D spending.
Table 1.1 New molecular entities: applications and approvals.
Figure 1.2 Drug development pathway.
Figure 1.3 Preapproval capitalized cost per approved NME.
Figure 1.4 Some definitions of translational research.
Figure 1.5 Sources of funding and support for translational research and development.
Table 1.2 Three dimensions of the critical path.
Figure 1.6 Sampling of schools with programs related to medical product development.
Figure 2.1 Product development planning is an integrative approach.
Figure 2.2 Product development planning.
Table 3.1 Chronology of significant regulations relevant to healthcare product development.
Figure 3.1 Examples of recent FDA initiatives affecting product development.
Table 4.1 Not all products of biological source are regulated by CBER.
Figure 4.1 Definition of a drug.
Figure 4.2a Minimum information included in an IND.
Figure 4.2b Clinical trial testing phases.
Figure 4.3 Definition of a biological product.
Figure 4.4 Definition of a medical device.
Figure 4.5 Minimum information included in an IDE.
Figure 4.6 Definition of a combination product.
Table 4.2 Number of original drug and biologics applications filed with CDER and CBER.
Table 4.3 Major medical device submissions received by CDRH.
Table 4.4 Examples of NMEs approved in 2011.
Table 4.5 Some recent biologics approvals.
Table 4.6 Recent medical device approvals and clearances.
Table 5.1 Examples of U.S. national class action product liability settlements.
Figure 5.1 Establishing product defects for product liability.
Figure 5.2 Responsibilities of product development planning in minimizing future product liability problems.
Figure 5.3 Primary considerations for product development planning.
Figure 6.1 Phases of clinical testing.
Figure 6.2 Mean time (months) from receipt to approval of priority NDA/BLA submissions.
Figure 6.3 Medical device classification panels.
Figure 6.4 Examples of reserved Class I devices.
Figure 7.1 The 1-10-100 rule.
Figure 7.2 Class I devices subject to design controls.
Figure 7.3 Examples of items to include in a design controls checklist.
Figure 8.1 Examples of potential interactions of risk elements.
Figure 8.2 Objectives of risk assessment and management.
Figure 8.3 Example of FMECA matrix.
Table 9.1 Examples of safety-based withdrawals of product approvals.
Figure 9.1 CDER recall statistics.
Figure 9.2 CDRH recall statistics.
Figure 9.3 CBER recall statistics.
Table 10.1 Outline of device HFE/UE report.
Figure 10.1 CDRH comments on human factors.
Figure 10.2 Examples of FDA publications on the topic of human factors.
Table 10.2 Examples of easily confused drug names.
Figure 10.3 Examples of general questions relative to demography and products.
Table 11.1 Initial evaluation tests for consideration: biological evaluation of medical devices.
Table 11.2 Supplementary evaluation tests for consideration: biological evaluation of medical devices.
Figure 11.1 Principles of ICH GCP.
Figure 11.2 Drug development pathway.
Figure 11.3 Diagrammatic representation of the ICH Common Technical Document.
Table 12.1 Common pharmacoeconomic methods.
Table 12.2 Examples of quality-of-life domains.
Figure 12.1 Questions applicable to CER.
Figure 13.1 S