A comprehensive look at existing technologies and processes for continuous manufacturing of pharmaceuticals As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process manufacturing provides a proven solution. Among its many benefits are: minimized waste, energy consumption, and raw material use; the accelerated introduction of new drugs; the use of smaller production facilities with lower building and capital costs; the ability to monitor drug quality on a continuous basis; and enhanced process reliability and flexibility. Continuous Manufacturing of Pharmaceuticals prepares professionals to take advantage of that exciting new approach to improving drug manufacturing efficiency. This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and protein/peptide products. The following section is devoted to process analytical tools for continuously operating manufacturing environments. The final two sections treat the integration of several individual parts of processing into fully operating continuous process systems and summarize state-of-art approaches for innovative new manufacturing principles. Brings together the essential know-how for anyone working in drug manufacturing, as well as chemical, food, and pharmaceutical scientists working on continuous processing Covers chemical engineering principles, regulatory aspects, primary and secondary manufacturing, process analytical technology and quality-by-design Contains contributions from researchers in leading pharmaceutical companies, the FDA, and academic institutions Offers an extremely well-informed look at the most promising future approaches to continuous manufacturing of innovative pharmaceutical products Timely, comprehensive, and authoritative, Continuous Manufacturing of Pharmaceuticals is an important professional resource for researchers in industry and academe working in the fields of pharmaceuticals development and manufacturing.

With contributions from biotechnologists and bioengineers, this ready reference describes the state of the art in industrial biopharmaceutical production, with a strong focus on continuous processes. Recent advances in single-use technology as well as application guidelines for all types of biopharmaceutical products, from vaccines to antibodies, and from bacterial to insect to mammalian cells are covered. The efficiency, robustness, and quality control of continuous production processes for biopharmaceuticals are reviewed and compared to traditional batch processes for a range of different production systems.

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 advanced 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.

On July 30-31, 2018, the National Academies of Sciences, Engineering, and Medicine held a workshop titled Continuous Manufacturing for the Modernization of Pharmaceutical Production. This workshop discussed the business and regulatory concerns associated with adopting continuous manufacturing techniques to produce biologics such as enzymes, monoclonal antibodies, and vaccines. The participants also discussed specific challenges for integration across the manufacturing system, including upstream and downstream processes, analytical techniques, and drug product development. The workshop addressed these challenges broadly across the biologics domain but focused particularly on drug categories of greatest FDA and industrial interest such as monoclonal antibodies and vaccines. This publication summarizes the presentations and discussions from the workshop.

This is the most comprehensive treatise of this topic available, providing invaluable information on the technological and economic benefits to be gained from implementing continuous processes in the biopharmaceutical industry. Top experts from industry and academia cover the latest technical developments in the field, describing the use of single-use technologies alongside perfusion production platforms and downstream operations. Special emphasis is given to process control and monitoring, including such topics as 'quality by design' and automation. The book is supplemented by case studies that highlight the enormous potential of continuous manufacturing for biopharmaceutical production facilities.

Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing Explore new trends in continuous biomanufacturing with contributions from leading practitioners in the field With the increasingly widespread acceptance and investment in the ??technology, the last decade has demonstrated the utility of continuous ??processing in the pharmaceutical industry. In Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing, distinguished biotechnologist Dr. Ganapathy Subramanian delivers a comprehensive exploration of the potential of the continuous processing of biological products and discussions of future directions in advancing continuous processing to meet new challenges and demands in the manufacture of therapeutic products. A stand-alone follow-up to the editor’s Continuous Biomanufacturing: Innovative Technologies and Methods published in 2017, this new edited volume focuses on critical aspects of process intensification, process control, and the digital transformation of biopharmaceutical processes. In addition to topics like the use of multivariant data analysis, regulatory concerns, and automation processes, the book also includes: Thorough introductions to capacitance sensors to control feeding strategies and the continuous production of viral vaccines Comprehensive explorations of strategies for the continuous upstream processing of induced microbial systems Practical discussions of preparative hydrophobic interaction chromatography and the design of modern protein-A-resins for continuous biomanufacturing In-depth examinations of bioprocess intensification approaches and the benefits of single use for process intensification Perfect for biotechnologists, bioengineers, pharmaceutical engineers, and process engineers, Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing is also an indispensable resource for chemical engineers seeking a one-stop reference on continuous biomanufacturing.

Process Systems Engineering for Pharmaceutical Manufacturing: From Product Design to Enterprise-Wide Decisions, Volume 41, covers the following process systems engineering methods and tools for the modernization of the pharmaceutical industry: computer-aided pharmaceutical product design and pharmaceutical production processes design/synthesis; modeling and simulation of the pharmaceutical processing unit operation, integrated flowsheets and applications for design, analysis, risk assessment, sensitivity analysis, optimization, design space identification and control system design; optimal operation, control and monitoring of pharmaceutical production processes; enterprise-wide optimization and supply chain management for pharmaceutical manufacturing processes. Currently, pharmaceutical companies are going through a paradigm shift, from traditional manufacturing mode to modernized mode, built on cutting edge technology and computer-aided methods and tools. Such shifts can benefit tremendously from the application of methods and tools of process systems engineering. - Introduces Process System Engineering (PSE) methods and tools for discovering, developing and deploying greener, safer, cost-effective and efficient pharmaceutical production processes - Includes a wide spectrum of case studies where different PSE tools and methods are used to improve various pharmaceutical production processes with distinct final products - Examines the future benefits and challenges for applying PSE methods and tools to pharmaceutical manufacturing

A guide to the important chemical engineering concepts for the development of new drugs, revised second edition The revised and updated second edition of Chemical Engineering in the Pharmaceutical Industry offers a guide to the experimental and computational methods related to drug product design and development. The second edition has been greatly expanded and covers a range of topics related to formulation design and process development of drug products. The authors review basic analytics for quantitation of drug product quality attributes, such as potency, purity, content uniformity, and dissolution, that are addressed with consideration of the applied statistics, process analytical technology, and process control. The 2nd Edition is divided into two separate books: 1) Active Pharmaceutical Ingredients (API’s) and 2) Drug Product Design, Development and Modeling. The contributors explore technology transfer and scale-up of batch processes that are exemplified experimentally and computationally. Written for engineers working in the field, the book examines in-silico process modeling tools that streamline experimental screening approaches. In addition, the authors discuss the emerging field of continuous drug product manufacturing. This revised second edition: Contains 21 new or revised chapters, including chapters on quality by design, computational approaches for drug product modeling, process design with PAT and process control, engineering challenges and solutions Covers chemistry and engineering activities related to dosage form design, and process development, and scale-up Offers analytical methods and applied statistics that highlight drug product quality attributes as design features Presents updated and new example calculations and associated solutions Includes contributions from leading experts in the field Written for pharmaceutical engineers, chemical engineers, undergraduate and graduation students, and professionals in the field of pharmaceutical sciences and manufacturing, Chemical Engineering in the Pharmaceutical Industry, Second Edition contains information designed to be of use from the engineer's perspective and spans information from solid to semi-solid to lyophilized drug products.

A practical guide to Quality by Design for pharmaceutical product development Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Written by experts in the field, the text explores the QbD approach to product development. This innovative approach is based on the application of product and process understanding underpinned by a systematic methodology which can enable pharmaceutical companies to ensure that quality is built into the product. Familiarity with Quality by Design is essential for scientists working in the pharmaceutical industry. The authors take a practical approach and put the focus on the industrial aspects of the new QbD approach to pharmaceutical product development and manufacturing. The text covers quality risk management tools and analysis, applications of QbD to analytical methods, regulatory aspects, quality systems and knowledge management. In addition, the book explores the development and manufacture of drug substance and product, design of experiments, the role of excipients, multivariate analysis, and include several examples of applications of QbD in actual practice. This important resource: Covers the essential information about Quality by Design (QbD) that is at the heart of modern pharmaceutical development Puts the focus on the industrial aspects of the new QbD approach Includes several illustrative examples of applications of QbD in practice Offers advanced specialist topics that can be systematically applied to industry Pharmaceutical Quality by Design offers a guide to the principles and application of Quality by Design (QbD), the holistic approach to manufacturing that offers a complete understanding of the manufacturing processes involved, in order to yield consistent and high quality products.

This book deals with various unique elements in the drug development process within chemical engineering science and pharmaceutical R&D. The book is intended to be used as a professional reference and potentially as a text book reference in pharmaceutical engineering and pharmaceutical sciences. Many of the experimental methods related to pharmaceutical process development are learned on the job. This book is intended to provide many of those important concepts that R&D Engineers and manufacturing Engineers should know and be familiar if they are going to be successful in the Pharmaceutical Industry. These include basic analytics for quantitation of reaction components– often skipped in ChE Reaction Engineering and kinetics books. In addition Chemical Engineering in the Pharmaceutical Industry introduces contemporary methods of data analysis for kinetic modeling and extends these concepts into Quality by Design strategies for regulatory filings. For the current professionals, in-silico process modeling tools that streamline experimental screening approaches is also new and presented here. Continuous flow processing, although mainstream for ChE, is unique in this context given the range of scales and the complex economics associated with transforming existing batch-plant capacity. The book will be split into four distinct yet related parts. These parts will address the fundamentals of analytical techniques for engineers, thermodynamic modeling, and finally provides an appendix with common engineering tools and examples of their applications.