【正文】 i 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 (/39。) revise the text with current and emerging sterile product development and manufacturing science and (ii) maintain the high standard of quality the readers expect. The third edition not only reflects enhanced content in all the chapters, but also more than half of the chapters are new underscoring the rapidly advancing technology. We have divided the volumes into logical subunits—volume 1 addresses formulation and packaging aspects。 volume 2, facility design, sterilization and processing。 and volume 3, regulations, validation and future directions. The authors invited to contribute chapters are established leaders with proven track records in their specialty areas. Hence, the textbook is authoritative and contains much of the collective experience gained in the (bio)pharmaceutical industry over the last two decades. We are deeply grateful to all the authors who made this work possible. Volume 1 begins with a historical perspective of injectablc drug therapy and mon routes of administration. Formulation of small molecules and large molecules is presented in depth, including ophthalmic dosage forms. Parenteral packaging options are discussed relative to glass and plastic containers, as well as elastomeric closures. A definitive chapter is provided on container closure integrity. Volume 2 presents chapters on facility design, cleanroom operations, and control of the chapter discussing pharmaceutical water systems is included. Key quality attributes of sterile dosage forms are discussed, including particulate matter, endotoxin, and sterility testing. The most widely used sterilization techniques as well as processing technologies are presented. Volume 2 concludes with an indepth chapter on lyophilization. Volume 3 focuses on regulatory requirements, riskbased process design, specifications, QbD, and extractables/leachables. In addition, we have included chapters on parenteral administration devices, siRNA delivery systems, injection site pain assessment, and control, PAT, and rapid microbiology test methods. Volume 3 concludes with a forwardlooking chapter discussing the future of parenteral product manufacturing. These three volumes differ from other textbooks in that they provide a learned review on developing parenteral dosage forms for both small molecules and biologies. Practical guidance is provided, in addition to theoretical aspects, for how to bring a drug candidate forward from discovery, through preclinical and clinical development, manufacturing, validation, and eventual registration. 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.