【正文】 gistration. The editors wish to thank Judy Clarkston and Lynn OTooleBird (Pfizer, Inc.) for their invaluable assistance and organizational support during this project, and Sherri Niziolek and Bianca Turnbull (Informa Healthcare) for patiently leading us through the publishing process. PREFACE We also acknowledge the assistance of Pfizer, Inc. colleagues Lin Chen and Min Huang for reviewing several of the chapters. We would like to express special gratitude to the late Kenh E. Avis (University of Tennessee College of Pharmacy) for his dedication to teaching and sharing practical knowledge in the area of parenteral medications to so many students over the years, including us. Finally, we acknowledge the contributions of Dr Avis, Leon Lachman, and Herbert A. Lieberman who edited the earlier editions of this book series. Sandeep Netna John D. LudwigContents Foreword Michael J. Akers vii Preface ix Contributors xiii 1. Aseptic manufacturing facility design 1 Mark Caldwell, Bob Helt, Beth Holden, Francesca McBride, and Kevin Schreier 2. Personnel and their impact on clean room operations 56 Jeanne Moldenhauer 3. The fundamentals of an environmental control program 80 William H. Miele 4. Water systems for parenteral facilities 91 Joseph /. Manfredi 5. Particulate matter: subvisible 114 D. Scott Aldrich 6. Endotoxin testing 146 Michael E. Dawson 7. The pendial sterility tests 187 Scott . Sutton 8. Industrial sterilization technologies: principles and overview 195 Anne F. Booth 9. Steam sterilization 221 James AgaHoco 10. Gas, vapor, and liquid chemical sterilization 241 fames Agalloco 11. Dry heat depyrogenation and sterilization 255 Deborah Havlik and Kevin Trupp 12. Radiation sterilization 268 Barry P. Fairand and Dusan Razemxii CONTENTS 13. Filters and filtration 297 Maik \N. Jornitz and Theodore H. Meltzer 14. Processing of small volume parenterals and large volume parenterals 334 Donald A. Eiseiihauer, Roland Schmidt, Christine Martin, and Steven G. Schultz 15. Freezedrying: principles and practice 353 Steven L. Nail and Larri/ A. Gatlin Index 383Contributors James Agalloco Agalloco amp。D Microbiology, Hospira, Inc., Lake Forest, Illinois, . Bob Helt Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Beth Holden Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Maik W. Jornitz Sartorius Stedim North America, Inc., Bohemia, New York, . Joseph J. Manfredi GMP Systems, Inc., Fairfield, New Jersey, . Christine Martin Abbott GmbH amp。s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures, or diagnoses should be independently verified. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the mt^ica 】 professional to make his or her own professional judgements, so as appropriately to advise and treat patients. Save for death or personal injury caused by the publisher39。 tradition. Their oversight of this third edition is work that their mentor would be highly pleased and proud of. From 29 chapters in the second edition to 43 chapters in this new edition, this threevolume series prehensively covers both the traditional subjects in parenteral science and technology as well as new and expanded subjects. For example, separate chapter topics in this edition not found in previous editions include solubility and solubilization, depot delivery systems, biophysical and biochemical characterization of peptides and proteins, container closure integrity testing, water systems, endotoxin testing, focused chapters on different sterilization methods, risk assessment in aseptic processing, visual inspection, advances in injection devices, RNAi delivery, regulatory considerations for excipients, techniques to evaluate pain on injection, product specifications, extractables and leachables, process analytical technology, and quality by design. The editors have done an outstanding job of convincing so many top experts in their fields to author these 43 chapters. The excellent reputations of the authors and editors of this book will guarantee superb content of each chapter. There is no other book in the world that covers the breadth and depth of parenteral science and technology better than this one. In my opinion, the editors have achieved their primary objectives—publishing a book that contains current and emerging sterile product development and manufacturing information, and maintaining the high standard of quality that readers would expect. Michael ]. Akers Baxter BioPhamia Solutions Bloomington, Indiana, .This page intentionally left blankPreface Pharmaceutical Dosage Forms: Parenteral Medications was originally published in 1984 and immediately accepted as a definitive reference in academic institutions and the pharmaceutical industry. The second edition was published in 1993. The ensuing years have produced incredible technological advancement. C lassic smallmolecule drugs are now plemented by plex molecules such as monoclonal antibodies, antibody fragments, aptamers, antisense, RNAi therapeutics, and DNA vaccines. There have been significant innovations in delivery devices, analytical techniques, insilico modeling, and manufacturing and control technologies. In addition, the global regulatory environment has shifted toward greater emphasis on sciencebased risk assessment as evidenced by the evolving cGMPs, quality by design (QbD), process analytical technology (PAT), continuous processing, real time release, and other initiatives. The rapidly changing landscape in the parenteral field was the primary reason we undertook the challenging task of updating the three volumes. Our objectives were to (/3