Process Understanding

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