Sources of Contamination in Medicinal Products and Medical Devices

579 Pages·2012·6.86 MB·English

by  Denise Bohrer(auth.)

SOURCES OF
CONTAMINATION IN
MEDICINAL PRODUCTS
AND MEDICAL
DEVICES
SOURCES OF
CONTAMINATION IN
MEDICINAL PRODUCTS
AND MEDICAL
DEVICES
DENISE BOHRER
Federal University of Santa Maria
Santa Maria, Brazil
A JOHN WILEY & SONS, INC., PUBLICATION
Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved
Published by John Wiley & Sons, Inc., Hoboken, New Jersey
Published simultaneously in Canada
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Library of Congress Cataloging-in-Publication Data:
Bohrer, Denise.
Sources of contamination in medicinal products and medical devices / Denise Bohrer.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-470-48750-1 (cloth)
1. Microbial contamination. 2. Pharmaceutical technology–Standards. 3. Pharmaceutical
industry–Quality control. I. Title.
RS192.B64 2012
338.4'76151–dc23
2012017302
Printed in the United States of America
ISBN: 9780470487501
10 9 8 7 6 5 4 3 2 1
A man will turn over half a library to make one book.
Samuel Johnson (English writer, 1709–1784)
This book is dedicated to my sons, Daniel and Marcelo,
and to the memory of my mother.
CONTENTS
PREFACE xv
ACKNOWLEDGMENTS xix
1 Introduction 1
Reference 6
2 Directives for Contamination Control 7
PART I CHEMICAL CONTAMINATION 17
3 Raw Materials 19
3.1 Water 19
3.2 Inorganic Impurities 27
3.3 Organic Impurities 32
3.3.1 By-products 32
3.3.2 Genotoxic Impurities (GTIs) 35
3.3.3 Degradation Products 39
3.4 Additives 52
3.5 Residual Solvents 58
Concluding Remarks 63
References 65
4 Medicinal Gases and Volatile Anesthetics 70
4.1 Medicinal Gases 70
4.2 Volatile Anesthetics 80
Concluding Remarks 93
References 94
ix
x COnTenTS
5 Diagnostic Imaging Agents 96
5.1 Radiopharmaceuticals 98
5.1.1 Technetium-Based Products 100
5.1.1.1 Production of Mo-99 100
5.1.1.2 Generation of Tc-99m 103
5.1.1.3 Labeling Procedures 107
5.1.2 Iodine-Based Products 113
5.1.3 Fluorine-Based Products 125
5.1.3.1 [18F]FDG Production and Labeling 127
5.1.3.2 Species Formed during [18O]H O
2
Irradiation 128
5.1.3.3 Residual Solvents and Components
Used in the Labeling 137
5.1.3.4 Radiolysis Products Generated by
elevated Activity of the Labeled
Compound 140
5.2 Contrast Agents 143
5.2.1 Gadolinium-Based Products 143
5.2.2 Iodine-Based Products 158
5.2.3 Barium Sulfate 172
Concluding Remarks 176
References 177
6 Containers 185
6.1 Glass Containers 185
6.2 Plastic Containers 199
6.2.1 Polymer Formation 199
6.2.2 PVC Containers 203
6.2.3 Other Plastic Containers 215
6.3 Metal Containers 220
Concluding Remarks 223
References 223
7 Closures 228
Concluding Remarks 256
References 256
8 Delivery Systems and Filters 259
8.1 Delivery Systems Made of PVC 260
8.2 Delivery Systems Made of Other Plastic Materials 275
8.3 Filters 282
Concluding Remarks 287
References 287
COnTenTS xi
9 Medical Devices 290
9.1 General Use Devices 293
9.1.1 Medical Gloves 294
9.1.2 Syringes 294
9.2 extracorporeal Circuits 300
9.3 Devices for Administration of Aerosolized Drugs 307
9.4 Reprocessed Medical Devices 308
9.5 Tissue Substitutes 309
9.5.1 Skin Substitutes and Surgical Dressings 310
9.5.2 Hard Tissue Substitutes 310
9.5.3 Soft Tissue Substitutes 311
Concluding Remarks 313
References 313
PART II PHYSICAL CONTAMINATION 317
10 Particulate Matter 319
Concluding Remarks 345
References 345
PART III MICROBIOLOGICAL CONTAMINATION 349
11 Microbiological and Endotoxin Contamination 351
11.1 Water 355
11.2 Raw Materials 361
11.3 Sterile Products 367
11.3.1 Single- and Multiple-Dose Products 368
11.3.2 Parenteral nutrition (Pn) 371
11.3.3 Propofol 378
11.3.4 Ophthalmic Products 384
11.4 Medicinal Gases 393
11.5 Medical Devices 394
11.5.1 Syringes 395
11.5.2 endoscopes 398
11.5.3 Other Devices 401
11.6 Biofilms 406
11.7 Dialysis Circuits 407
11.8 nosocomial Infections 413
Concluding Remarks 420
References 422
xii COnTenTS
PART IV MISCELLANEOUS 433
12 Contamination from Sterilization Procedures 435
12.1 Residuals from Radiation Sterilization 437
12.1.1 Radiolysis of Water 438
12.1.2 effect of Ionizing Radiation on Drug Products 439
12.1.3 Polymers in Drug Delivery 440
12.1.3.1 Polylactide (PLA) and
Poly(lactide-co-glycolide) (PLGA) 443
12.1.3.2 Collagen 448
12.1.3.3 Cellulose and Other Polysaccharides 448
12.1.3.4 Alginate 450
12.1.4 Radiolysis of Selected nondrug Components 450
12.1.4.1 Residual Solvents 450
12.1.4.2 Monosaccharides 451
12.1.4.3 Starch 451
12.1.5 effect of Ionizing Radiation on Materials Used in
Packaging and in Medical Devices 454
12.1.5.1 Ultra-High-Molecular-Weight
Polyethylene (UHMWPe) 456
12.1.5.2 Polyurethane (PU) 458
12.1.5.3 Silicone 464
12.1.5.4 Polyamide (PA) 464
12.1.5.5 Poly(methyl methacrylate) (PMMA) 466
12.1.5.6 Polytetrafluoroethylene (PTFe) 468
12.1.5.7 Polyvinyl Chloride (PVC) 468
12.1.5.8 Polyethylene (Pe) 470
12.1.5.9 Polypropylene (PP) 473
12.1.5.10 Polyethylene Terephthalate (PeT) 478
12.1.5.11 Polystyrene (PS) 478
12.1.5.12 Polysulfone (PSf) 478
12.1.5.13 ethylene Vinyl Acetate (eVA) 480
12.1.5.14 Multilayer Materials 482
12.2 Heat Sterilization 483
12.3 Residuals from Chemical Disinfection and
Sterilization Agents 486
12.3.1 ethylene Oxide (etO) 487
12.3.2 Peracetic Acid and Hydrogen Peroxide 494
12.3.3 Formaldehyde 497
Concluding Remarks 503
References 504
13 Biotechnological Products 512
13.1 DnA and HCP Residuals 516
13.2 Viruses and Mycoplasma 516
COnTenTS xiii
13.3 endotoxin 518
13.4 Protein Degradation 522
13.5 Protein Aggregation 524
Concluding Remarks 530
References 530
Appendix Polymeric Materials: Components, Additives,
Extractables, and Degradation Products 533
References 553
INDEX 555