Combination Products: Regulatory Challenges and Successful Product Development

260 Pages·2008·1.67 MB·English

by  Smita Gopalaswamy

COMBINATION
PRODUCTS
Regulatory Challenges
and
Successful Product Development
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COMBINATION
PRODUCTS
Regulatory Challenges
and
Successful Product Development
Smita Gopalaswamy • Venky Gopalaswamy
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
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International Standard Book Number-13: 978-1-4200-6446-9 (Hardcover)
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Library of Congress Cataloging-in-Publication Data
Gopalaswamy, Smita.
Combination products : regulatory challenges and successful product developement
/ Smita Gopalaswamy and Venky Gopalaswamy.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4200-6446-9 (hardcover : alk. paper)
1. Drugs--Standards--United States. 2. Medical instruments and
apparatus--Standards--United States. 3. Biological products--Standards--United
States. 4. United States. Food and Drug Administration. I. Gopalaswamy, Venky. II.
Title.
[DNLM: 1. United States. Food and Drug Administration. 2. Equipment
Design--standards--United States. 3. Pharmaceutical Preparations--standards--United
States. 4. Biological Products--standards--United States. 5. Device
Approval--standards--United States. 6. Equipment and Supplies--standards--United
States. QV 26 G659c 2008]
RM301.27.G68 2008
615’.1--dc22 2007043090
Visit the Taylor & Francis Web site at
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Dedication
To my late parents, who always encouraged me to do my best, all
my academic mentors, and colleagues in my professional journey.
—S. G.
To professionals in medical device, pharmaceutical,
and biologics industries working to successfully
develop and launch combination products.
—V. G.
v
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Contents
About the authors ................................................................................................xv
1 Introduction ......................................................................................................1
Market .............................................................................................................4
International potential ..................................................................................5
2 Overview of combination products .............................................................7
Combination product classifi cation ............................................................7
Novel drug delivery systems ..................................................................7
Traditional drug delivery systems .........................................................7
Drug-enhanced devices ...........................................................................8
Regenerative medicinal products ...........................................................8
Examples of combination products ............................................................8
Biologic-device combination product ..................................................10
Bioartifi cial organs (tissue engineered) ...............................................10
Recently approved combination products ...............................................10
Breath test combination products ........................................................12
Drug-device combination catheter lock/fl ush solutions ...................13
Biologic-device: Vitagel Surgical Hemostat ........................................14
Differently regulated constituent parts (drug, device, biological
product) ......................................................................................................14
Copackaged (21 CFR 3.2 (e)(2)) ..............................................................15
GMP guidance .............................................................................................15
European union (EU) defi nitions ..............................................................20
Bibliography .................................................................................................21
3 Ensuring successful combination
product development ....................................................................................23
Benefi ts of developing combination products .........................................23
The road map to achieve control of design ..............................................27
Establishing a development plan .........................................................28
Product development in healthcare product industries ........................30
Innovation domain .................................................................................30
Opportunity identifi cation (innovation and customer domain) .....33
vii
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viii Contents
Customer domain ...................................................................................34
The project charter..................................................................................35
Customer wants and needs: Design inputs
(customer domain) ...............................................................................37
Concept selection ....................................................................................40
Proof-of-concept testing .........................................................................41
Risk analysis and management ............................................................42
Functional domain ......................................................................................43
Management of design requirements (from initial design
inputs to fi nal design outputs) ...........................................................44
A systems engineering approach to
management of requirements ............................................................46
Initiating the requirements cascade (from the customer
domain to the functional domain) .....................................................47
Requirements cascade ............................................................................48
What is the difference between a requirement and a parameter? ..48
What is functional? .................................................................................49
From the functional domain to the design and process domains ..50
Stability studies .......................................................................................52
Design domain .............................................................................................53
Process analytical technology (PAT) ....................................................54
Governance ..............................................................................................55
Process domain ............................................................................................56
Technology transfer/scale-up ...............................................................56
Production scale-up ................................................................................56
Process development ..............................................................................57
Process validation ...................................................................................57
Supplier selection and qualifi cation.....................................................57
Transfer to operations ............................................................................58
Postmarket domain .....................................................................................58
Bibliography .................................................................................................62
4 Overview of FDA and other regulatory
agency expectations .......................................................................................63
Regulatory requirements for FDA/EU of combination products ........65
Regulation of combination products by FDA agency .......................69
Number of marketing applications for a combination product .......69
When one marketing application may be appropriate .....................70
When two marketing applications may be necessary.......................70
Flowcharts ....................................................................................................71
FDA agency: CDRH (devices) ....................................................................71
Examples of the regulatory pathway for several different
combination products ..........................................................................71
FDA interactions: early interaction and communication with
the FDA ..................................................................................................76
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Contents ix
Combination product regulation in the EU .............................................76
Mode of action .........................................................................................77
How are the regulations applied to combination products? ............78
The regulatory pathway for a drug-eluting stent in the EU .............81
Component 1: The bare-metal stent ................................................81
Component 2: The drug (active ingredient) ...................................81
Component 3: Drug delivery (carrier) .............................................82
Clinical studies ...................................................................................82
Investigation brochure ......................................................................82
Notifi ed body selection .....................................................................83
Design dossier ....................................................................................83
Global regulatory requirements ................................................................84
Canada .....................................................................................................84
Pharmaceuticals: Prescription and nonprescription drugs .........86
Medical devices ..................................................................................86
Medical Devices Bureau ...................................................................87
Combination products ......................................................................87
Classifi cation of drug–medical device combination
products by therapeutic products committee: decisions ...........88
Classifi cation examples of products ................................................88
Japan .........................................................................................................89
Medical devices ..................................................................................89
MHLW .................................................................................................93
Pharmaceutical and Medical Safety Bureau ..................................93
Division of drugs ...............................................................................95
Division of biological chemistry and biologicals ..........................95
Division of medical devices ..............................................................95
China ........................................................................................................95
Agencies and regulations .................................................................96
The State Food and Drug Administration (SFDA) ........................96
The SFDA department of medical devices .....................................97
SFDA departments .............................................................................97
India ..........................................................................................................99
The regulation of medical devices ................................................100
Information required to be included with the application
for a registration certifi cate in India ...........................................100
Bibliography ...............................................................................................103
5 Resource requirements ...............................................................................105
Resources ....................................................................................................105
Addition of a drug or biologic to a device ........................................107
Addition of a device to a biologic-device
combination product ..........................................................................108
Facilities ......................................................................................................110
In-house testing .........................................................................................110
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