List of Contributors.

1 Quality by Design (Vince McCurdy).

1.1 History.

1.2 Defining Product Design Requirements and Critical Quality Attributes.

1.3 The Role of Quality Risk Management in QbD.

1.4 Design Space and Control Strategy.

1.5 Quality Systems.

References.

2 Route and Process Selection (David J. Ager).

2.1 Introduction.

2.2 Route Evaluation.

2.3 Factors to Consider.

2.4 Route Selection.

2.5 Process Selection.

2.6 Summary.

References.

3 Critical Stages of Safety Assessment in Process Design and Scale-Up (Stephen Rowe).

3.1 Reaction Safety Concepts.

3.2 Pre-Laboratory Safety Studies.

3.3 The Synergies of Safety and Optimization – Together.

3.4 Establishing a Reliable Basis of Safety for Scale-Up.

3.5 Flammability Hazards.

3.6 Summary.

References.

4 Understanding the Reaction (John Atherton, Ian Houson, and Mark Talford).

4.1 Introduction.

4.2 Process Complexity.

4.3 Topics for Data Acquisition.

4.4 Reaction Profiles.

4.5 Reaction Pictures.

4.6 Ionic Equilibria and Reaction Selectivity.

4.7 Kinetics.

4.8 Catalyzed Processes.

4.9 The Rate-Determining Step.

4.10 Mixing in Chemical Reactors.

4.11 Mixing Theory.

4.12 Multiphase Processes.

4.13 Mass Transfer Theory.

4.14 Mass Transfer and Mixing Requirements in Multiphase Systems.

4.15 Concepts of Structure and Scale for Equipment Selection.

4.16 Conclusion.

References.

5 Use of Models to Enhance Process Understanding (Wilfried Hoffmann).

5.1 Introduction.

5.2 The Process Characterization Elements of a Chemical Reaction.

5.3 The Impact of Modeling.

5.4 Understanding the Chemistry.

5.5 Physical Rates (the Elements of Mass Transfer).

5.6 Summary and Outlook.

References.

6 Scale-Up of Chemical Reactions (E. Hugh Stitt and Mark J. H. Simmons).

6.1 Introduction.

6.2 Case Study – Batch Hydrogenation.

6.3 Scale-Up of Stirred Tank Reactors (STRs).

6.4 Stirred Tank Scale-Up.

6.5 Chemistry Effects in Scale-Up.

6.6 Achieving Process Understanding for Reactor Scale-Up.

6.7 Reactor Selection.

6.8 Exploiting Process Understanding in Scale-Up.

6.9 Conclusions.

References.

7 Process Understanding – Crystallization (Leroy Cronin, Philip J. Kitson, and Chick C. Wilson).

7.1 Introduction.

7.2 Crystallization Processes.

7.3 Batch Crystallization Techniques.

7.4 Process Control of Crystallization.

7.5 Analytical Techniques for Product Characterization.

7.6 Conclusions.

Acknowledgments.

References.

8 Key Technologies and Opportunities for Innovation at the Drug Substance–Drug Product Interface (Colm Campbell and Brian Keaveny).

8.1 Introduction.

8.2 Opportunities for Innovation.

8.3 Crystallization.

8.4 Selected Manufacturing Technologies at the Drug Substance–Drug Product Interface.

8.5 Analytical Techniques.

8.6 Conclusions.

Acknowledgments.

References.

9 Process Understanding Requirements in Established Manufacture (Dylan Jones).

9.1 Introduction.

9.2 The Status Quo.

9.3 Risk and Reward.

9.4 Terms and Definitions.

9.5 Process Understanding Requirements.

9.6 Method Development and Installation.

9.7 Statistical Process Control.

9.8 Automation.

9.9 Conclusion.

References.

10 Plant Design (Mark J. Dickson).

10.1 Introduction.

10.2 Developing Process Concept to Plant Concept.

10.3 Regulations.

10.4 Infrastructure Design.

10.5 Portfolio Analysis and Asset Planning.

11 Contract Manufacture (Steve Woolley).

11.1 Introduction.

11.2 Why Contract?

11.3 The Contractor.

11.4 The Client.

11.5 Technology Transfer.

11.6 What Makes a Good Technical Package?

11.7 Client Process Understanding.

11.8 Case Studies.

11.9 Winning and Delivering the Project.

11.10 Project Timing.

11.11 Challenges of Multiproduct Plant Scheduling against an Uncertain Background.

11.12 Conclusion.

12 Whole Process Design (Paul Sharratt).

12.1 Process Understanding for Whole Process Design.

12.2 Process Outcomes.

12.3 Organization of the Design Activity.

12.4 Risk and Uncertainty in WPD.

12.5 Whole Process Representations.

12.6 Decision Making in WPD.

12.7 Summary.

References.

Index.