Process Understanding is the underpinning knowledge that allows the manufacture of chemical entities to be carried out routinely, robustly and to the required standard of quality. This area has gained in importance over the last few years, particularly due to the recent impetus from the USA's Food and Drug Administration. This book covers the multidisciplinary aspects required for successful process design, safety, modeling, scale-up, PAT, pilot plant implementation, plant design as well the rapidly expanding area of outsourcing. In discussing what process understanding means to different disciplines and sectors throughout a product's life cycle, this handbook and ready reference reveals the factors important to the development and manufacture of chemicals. The book focuses on the fundamental scientific understanding necessary. for a smoother technical transfer between the disciplines, leading to more effective and effi cient process development and manufacturing. A range of case studies are used to exemplify and illustrate the main issues raised.
As a result, readers will appreciate that process understanding can deliver a real competitive advantage within the pharmaceuticals and fine chemicals industry. This book serves as an aid to meeting the stringent regulations required by the relevant authorities through demonstrable understanding of the underlying science.
Ian Houson gained a 1st class BSc. Hons in Chemistry and Oceanography from the University of Southampton, he completed his doctorate at the University of Oxford with Prof. John Brown FRS in organic chemistry. Ian then joined Zeneca, which became Avecia and finally NPIL Pharma where he was Chemical Process R&D Manager for the site. His main roles were invention of new routes, scale-up and manufacturing support for the contract manufacturing of agrochemicals and pharmaceuticals at the kg's to 10's tonnes scale. Moving to Britest Ltd. in 2007 as a senior innovation specialist, Ian was involved in developing new tools and methodologies for innovative process development and manufacturing, facilitating manufacturing process improvement studies and collaborative research in a number of European projects. In March 2011 Ian joined Giltech Ltd, Ayr, Scotland as a Senior Scientist involved in development of novel biodegradable and slow release technologies across a wide range of chemicals and medical device applications. His responsibilities include product development, supporting joint development projects and intellectual property aspects.
Preface QUALIT Y BY DESIGN History Defining Product Design Requirements and Critical Quality Attributes The Role of Quality Risk Management in QbD Design Space and Control Strategy Quality Systems ROUTE AND PROCESS SELECTION Introduction Route Evaluation Factors to Consider Route Selection Process Selection Summary CRITICAL STAGES OF SAFETY ASSESSMENT IN PROCESS DESIGN AND SCALE-UP Reaction Safety Concepts Pre-Laboratory Safety Studies The Synergies of Safety and Optimization - Together Establishing a Reliable Basis of Safety for Scale-Up Flammability Hazards Summary UNDERSTANDING THE REACTION Introduction Process Complexity Topics for Data Acquisition Reaction Profiles Reaction Pictures Ionic Equilibria and Reaction Selectivity Kinetics Catalyzed Processes The Rate-Determining Step Mixing in Chemical Reactors Mixing Theory Multiphase Processes Mass Transfer Theory Mass Transfer and Mixing Requirements in Multiphase Systems Concepts of Structure and Scale for Equipment Selection Conclusion USE OF MODELS TO ENHANCE PROCESS UNDERSTANDING Introduction The Process Characterization Elements of a Chemical Reaction The Impact of Modeling Understanding the Chemistry Physical Rates (The Elements of Mass Transfer) Summary and Outlook SCALE-UP OF CHEMICAL REACTIONS Introduction Case Study - Batch Hydrogenation Scale-Up of Stirred Tank Reactors (STRs) Stirred Tank Scale-Up Chemistry Effects in Scale-Up Achieving Process Understanding for Reactor Scale-Up Reactor Selection Exploiting Process Understanding in Scale-Up Conclusions PROCESS UNDERSTANDING - CRYSTALLIZATION Introduction Crystallization Processes Batch Crystallization Techniques Process Control of Crystallization Analytical Techniques for Product Characterization Conclusions KEY TECHNOLOGIES AND OPPORTUNITIES FOR INNOVATION AT THE DRUG SUBSTANCE - DRUG PRODUCT INTERFACE Introduction Opportunities for Innovation Crystallization Selected Manufacturing Technologies at the Drug Substance - Drug Product Interface Analytical Techniques Conclusions PROCESS UNDERSTANDING REQUIREMENTS IN ESTABLISHED MANUFACTURE Introduction The Status Quo Risk and Reward Terms and Definitions Process Understanding Requirements Method Development and Installation Statistical Process Control Automation Conclusion PLANT DESIGN Introduction Developing Process Concept to Plant Concept Regulations Infrastructure Design Portfolio Analysis and Asset Planning CONTRACT MANUFACTURE Introduction Why Contract? The Contractor The Client Technology Transfer What Makes a Good Technical Package? Client Process Understanding Case Studies Winning and Delivering the Project Project Timing Challenges of Multiproduct Plant Scheduling against an Uncertain Background Conclusion WHOLE PROCESS DESIGN Process Understanding for Whole Process Design Process Outcomes Organization of the Design Activity Risk and Uncertainty in WPD Whole Process Representations Decision Making in WPD Summary