Continuous Pharmaceutical Processing

Continuous pharmaceutical manufacturing is currently receiving much interest from industry and regulatory authorities, with the joint aim of allowing rapid access of novel therapeutics and existing medications to the public, without compromising high quality. Research groups from different academic institutions have significantly contributed to this field with an immense amount of published research addressing a variety of topics related to continuous processing. The book is structured to have individual chapters on the different continuous unit operations involved in drug substance and drug product manufacturing. A wide spectrum of topics are covered, including basic principles of continuous manufacturing, applications of continuous flow chemistry in drug synthesis, continuous crystallization, continuous drying, feeders and blenders, roll compaction and continuous wet granulation.The underlying theme for each of these chapters is to present to the reader the recent advances in modePharmaceuticals -- Regulatory Considerations for Continuous Manufacturing. ling, experimental investigations and equipment design as they pertain to each individual unit operation. The book also includes chapters on quality by design (QbD) and process analytical technology (PAT) for continuous processing, process control strategies including new concepts of quality-by-control (QbC), real-time process management and plant optimization, business and supply chain considerations related to continuous manufacturing as well as safety guidelines related to continuous chemistry. A separate chapter is dedicated to discussing regulatory aspects of continuous manufacturing, with description of current regulatory environment quality/GMP aspects, as well as regulatory gaps and challenges. Our aim from publishing this book is to make it a valuable reference for readers interested in this topic, with a desire to gain a fundamental understanding of engineering principles and mechanistic studies utilized in understanding and developing continuous processes. In addition, our auticals -- Regulatory Considerations for Continuous Manufacturing. dva nced readers and practitioners in this field will find that the technical content of Continuous Pharmaceutical Processing is at the forefront of recent technological advances, with coverage of future prospects and challenges for this technology Front Matter ....Pages i-viii Basic Principles of Continuous Manufacturing (Sudarshan Ganesh, Gintaras V. Reklaitis)....Pages 1-21 Continuous Reactors for Pharmaceutical Manufacturing (Martin D. Johnson, Scott A. May, Michael E. Kopach, Jennifer Mc Clary Groh, Timothy Donald White, Kevin P. Cole et al.)....Pages 23-50 Understanding Residence Time, Residence Time Distribution, and Impact of Surge Vessels (Martin D. Johnson, Scott A. May, Jennifer Mc Clary Groh, Luke P. Webster, Vaidyaraman Shankarraman, Richard D. Spencer et al.)....Pages 51-85 Intermittent Flow and Practical Considerations for Continuous Drug Substance Manufacturing (Martin D. Johnson, Scott A. May, Jennifer McClary Groh, Timothy Braden, Richard D. Spencer)....Pages 87-127 Continuous Crystallization: Equipment and Operation (Yiqing C. Liu, Zoltan K. Nagy)....Pages 129-192 Continuous Feeding-Blending in Pharmaceutical Continuous Manufacturing (Qinglin Su, Gintaras V. Reklaitis, Zoltan K. Nagy)....Pages 193-226 Recent Progress in Roll Compaction Process Development for Pharmaceutical Solid Dosage Form Manufacture (Ariel R. Muliadi, Alamelu Banda, Chen Mao)....Pages 227-267 Continuous Wet Granulation (Arwa El Hagrasy, Li Ge Wang, Jim Litster)....Pages 269-300 Continuous Fluidized Bed Drying: Advanced Modeling and Experimental Investigations (Ibrahim Alaathar, Stefan Heinrich, Ernst-Ulrich Hartge)....Pages 301-359 Statistical Methods in Quality by Design and Process Analytical Technologies for Continuous Processes to Enable Real-Time Release (Vanessa Cárdenas, Juan G. Rosas, Carlos Pinzón, Rodolfo J. Romañach)....Pages 361-393 Active Process Control in Pharmaceutical Continuous Manufacturing – The Quality by Control (QbC) Paradigm (Qinglin Su, Sudarshan Ganesh, Gintaras V. Reklaitis, Zoltan K. Nagy)....Pages 395-427 Real-Time Optimization: How to Change Setpoints in Pharmaceutical Manufacturing (Arun Giridhar, Gintaras V. Reklaitis)....Pages 429-440 Safety Guidelines for Continuous Processing (Martin D. Johnson, Jeffry Niemeier)....Pages 441-476 Evaluating the Business Case for Continuous Manufacturing of Pharmaceuticals: A Supply Network Perspective (Jagjit Singh Srai, Ettore Settanni, Parminder Kaur Aulakh)....Pages 477-512 Regulatory Considerations for Continuous Manufacturing (Elaine Morefield)....Pages 513-535 Back Matter ....Pages 537-541 Continuous pharmaceutical manufacturing is currently receiving much interest from industry and regulatory authorities, with the joint aim of allowing rapid access of novel therapeutics and existing medications to the public, without compromising high quality. Research groups from different academic institutions have significantly contributed to this field with an immense amount of published research addressing a variety of topics related to continuous processing. The book is structured to have individual chapters on the different continuous unit operations involved in drug substance and drug product manufacturing. A wide spectrum of topics are covered, including basic principles of continuous manufacturing, applications of continuous flow chemistry in drug synthesis, continuous crystallization, continuous drying, feeders and blenders, roll compaction and continuous wet granulation. The underlying theme for each of these chapters is to present to the reader the recent advances in modeling, experimental investigations and equipment design as they pertain to each individual unit operation. The book also includes chapters on quality by design (QbD) and process analytical technology (PAT) for continuous processing, process control strategies including new concepts of quality-by-control (QbC), real-time process management and plant optimization, business and supply chain considerations related to continuous manufacturing as well as safety guidelines related to continuous chemistry. A separate chapter is dedicated to discussing regulatory aspects of continuous manufacturing, with description of current regulatory environment quality/GMP aspects, as well as regulatory gaps and challenges. Our aim from publishing this book is to make it a valuable reference for readers interested in this topic, with a desire to gain a fundamental understanding of engineering principles and mechanistic studies utilized in understanding and developing continuous processes. In addition, our adva nced readers and practitioners in this field will find that the technical content of Continuous Pharmaceutical Processing is at the forefront of recent technological advances, with coverage of future prospects and challenges for this technology