Page 12 - Chiral Separation Techniques

XII Contents

10 The Use of SMB for the Manufacture of Enantiopure Drug
Substances: From Principle to cGMP Compliance 255
S. R. Perrin, R. M. Nicoud

10.1 Introduction 255
10.1.1 FDA as the Driving Force: (Enantiopure Drugs and
Compliance) 255
10.1.1.1 Market Exclusivity: Newly Approved Drug Substances 256
10.1.1.2 Fixed-Combination Dosage: Enantiopure Drug Substances 256
10.1.1.3 Pharmaceutical Industry: Mergers 257
10.2 Chromatographic Processes 258
10.2.1 SMB: Comparisons to Batch Chromatography 258
10.2.2 Illustrations of SMB Processes 259
10.3 SMB as a Development Tool 260
10.3.1 Basic Principles and Technical Aspects 260
10.3.2 Operating Conditions 264
10.3.2.1 Step A: Aquisition of Relevant Physico-Chemical Parameters 264
10.3.2.2 Step B: Calculation of TMB 266
10.3.2.3 Step C: Calculation of SMB 269
10.4 Example of Process Design 269
10.4.1 Manufacture of Enatiopure Drug Substances 269
10.4.1.1 Gathering Physico-Chemical Parameters 270
10.4.1.2 SMB: Linear Conditions 272
10.4.1.3 SMB: Nonlinear Conditions 275
10.5 SMB as a Production Tool 277
10.5.1 cGMP Compliance 277
10.5.1.1 Manufacturing and Process Controls 277
10.5.1.2 Solvent Recovery 278
10.5.1.3 In-Process Testing 279
10.5.1.4 Calculation of Yields and Definition of Batch 279
10.5.2 Process Validation 279
10.6 SMB Accepted for Manufacturing 283
10.6.1 Practical Implications for Manufacturing 283
10.7 Conclusions 283
References 284

11 Electrophoretically-driven Preparative Chiral Separations using
Cyclodextrins 289
A. M. Stalcup

11.1 Introduction 289
11.2 Classical Electrophoretic Chiral Separations: Batch Processes 291
11.3 Classical Electrophoretic Chiral Separations: Continuous
Processes 294