Scale-Up and Optimization in Preparative Chromatography: Principles and Biopharmaceutical Applications (Chromatographic Science)

✍ Scribed by Ajoy Velayudhan

• Publisher: CRC Press
• Year: 2002
• Tongue: English
• Leaves: 346
• Edition: 1
• Category: Library

✦ Synopsis

Presenting guidelines for predicting and improving separation system performance, this book contains numerous case studies illustrating the practice of scale-up principles in process development. It offers solutions to limitations that occur in real-world purification schemes; methods to model, optimize, and characterize nonlinear separation processes; data comparisons from all stages of production; and industrial separation schemes for products such as synthetic molecules, antibody fragments, IgG, growth factors, and plasmid DNA. The book covers external constraints, separation economics, correlations for transport and kinetic phenomena, and the configuration and parameters of column design.

✦ Table of Contents

SCALE-UP AND OPTIMIZATION IN PREPARATIVE CHROMATOGRAPHY......Page 1
PREFACE......Page 7
CONTRIBUTORS......Page 12
CONTENTS......Page 10
I. INTRODUCTION......Page 15
CONTENTS......Page 0
B. OPTIMIZATION OF THERMODYNAMICS AT BENCH SCALE......Page 17
A. PHYSICAL OVERVIEW......Page 26
B. SIMPLE SCALE-UP CALCULATION......Page 29
C. CONSTANCY OF PHASE RATIO WITH SCALE......Page 33
A. PRACTICAL GUIDELINES......Page 34
B. OTHER MODES OF OPERATION......Page 38
C. PRACTICAL CONSIDERATIONS FOR MODES OF INTERACTION......Page 39
V. CONCLUSIONS......Page 42
REFERENCES......Page 43
I. INTRODUCTION......Page 47
A. GENERIC ECONOMIC CHARACTERISTICS......Page 48
B. PROCESS DESIGN STRATEGY......Page 49
III. MASS TRANSFER HEURISTICS......Page 52
IV. ESTABLISHING THE CHROMATOGRAPHIC FAMILY......Page 54
V. DIFFERENTIAL CHROMATOGRAPHY AND HEIGHTS OF A THEORETICAL PLATE......Page 60
VI. TIME CONSTANTS AND PROCESS OPERATIONS......Page 69
VII. DEVIATIONS FROM SIMPLE MODELS......Page 73
A. REVERSIBILITY VS. IRREVERSIBILITY AND DETECTION OF FLOW MALDISTRIBUTION......Page 74
B. MODELING OF ACTUAL SYSTEMS......Page 76
VIII. CONCLUDING REMARKS......Page 82
NOMENCLATURE......Page 83
APPENDIX A ADDITIVITY OF MOMENTS......Page 85
REFERENCES......Page 87
I. INTRODUCTION......Page 90
II. DEFINITIONS......Page 91
III. COLUMN CHARACTERISTICS......Page 93
A. ADSORPTION ISOTHERMS......Page 94
IV. OBJECTIVE FUNCTIONS......Page 95
A. THE IDEAL MODEL OF CHROMATOGRAPHY......Page 96
B. EQUILIBRIUM-DISPERSIVE MODEL......Page 101
C. THE PARAMETERS TO BE OPTIMIZED......Page 104
D. OPTIMIZATION FOR MAXIMUM PRODUCTION RATE AND MAXIMUM PR Y......Page 110
E. OPTIMIZATION FOR MAXIMUM SPECI.C PRODUCTION......Page 120
VI. COMPARING THE PERFORMANCE OF THE DIFFERENT MODES OF PREPARATIVE CHROMATOGRAPHY......Page 125
REFERENCES......Page 132
I. MECHANISM OF ION-EXCHANGE CHROMATOGRAPHY......Page 135
A. DISTRIBUTION COEFFICIENT......Page 136
II. DEVELOPMENT OF AN IMPROVED SEPARATION......Page 137
III. SCALE-UP OF AN OPTIMIZED SEPARATION......Page 138
A. MODEL DERIVATION......Page 140
B. GH–IR CURVES......Page 146
C. DETERMINATION OF THE K–I CURVE......Page 148
D. USE THE MODEL FOR SCALE-UP TO AN INDUSTRIAL SIZE COLUMN......Page 150
E. USE OF THE MODEL FOR LINEAR GRADIENT ELUTION OPTIMIZATION......Page 152
F. USE OF THE MODEL TO IMPROVE PRODUCTIVITY......Page 157
V. CHARACTERIZATION AND TROUBLESHOOTING OF THE SEPARATION......Page 158
VI. DISPERSION IN CHROMATOGRAPHY—HETP......Page 162
A. CALCULATION OF HETP FROM RESIDENCE TIME DISTRIBUTION CURVES......Page 166
B. HETP VALUES IN FIXED BED CHROMATOGRAPHY......Page 167
VII. PRESSURE DROP IN FIXED BED CHROMATOGRAPHY......Page 170
NOMENCLATURE......Page 176
REFERENCES......Page 179
I. INTRODUCTION......Page 184
A. TRUE MOVING BEDS......Page 186
B. SIMULATED MOVING BEDS......Page 189
A. SOLID FLOW”......Page 191
B. FLUID FLOWS......Page 192
C. DESIGN FLOWS......Page 193
IV. OPERATING AN SMB UNDER DILUTE, OR LINEAR, CONDITIONS......Page 194
A. DETERMINATION OF THE DISTRIBUTION COEFFICIENTS KA AND KB......Page 196
B. SELECTION OF THE COLUMN SWITCHING TIME......Page 197
C. SELECTING THE OPERATING FLOW RATES......Page 198
D. STEADY STATE......Page 200
A. SINGLE-UNIT FAILURES......Page 201
B. TWO-UNIT FAILURES......Page 202
A. CONTROL......Page 206
B. DESIGN AND OPTIMIZATION......Page 207
VII. ECONOMICS OF SMB OPERATION......Page 208
IX. CONCLUDING REMARKS......Page 210
REFERENCES......Page 211
I. INTRODUCTION......Page 213
II. CONTACTING OPERATIONS......Page 214
III. COLUMN CHROMATOGRAPHY......Page 215
IV. FEEDSTOCK......Page 216
V. ANION-EXCHANGE CHROMATOGRAPHY OF HEN EGG WHITE PROTEINS......Page 217
VI. COLUMN DESIGN......Page 220
B. FIXED VOLUME RADIAL FLOW......Page 222
C. FIXED VOLUME SIDE PACK AXIAL FLOW......Page 226
D. ADJUSTABLE VOLUME SLURRY PACK AXIAL FLOW......Page 229
E. ADJUSTABLE VOLUME PUMP PACK AXIAL FLOW......Page 232
VII. COMPARATIVE PERFORMANCE OF DIFFERENT COLUMN FORMATS......Page 235
REFERENCES......Page 237
I. INTRODUCTION......Page 240
II. ASSAYS, SEPARATION GOALS, AND SCALE-UP CONSIDERATIONS......Page 242
III. COLUMN SELECTION AND CAPACITY......Page 244
IV. DEVELOPMENT OF WASH AND ELUTION CONDITIONS......Page 249
V. OPERATION......Page 255
REFERENCES......Page 259
I. INTRODUCTION......Page 260
II. BACKGROUND......Page 261
C. SIZE EXCLUSION CHROMATOGRAPHY......Page 263
D. LIGHT SCATTERING......Page 264
G. HPLC ANION-EXCHANGE ASSAY......Page 265
A. LABORATORY SCALE STUDIES......Page 266
B. IMPLEMENTATION AND SCALE-UP......Page 275
REFERENCES......Page 279
II. DESCRIPTION OF UPSTREAM PROCESS......Page 282
III. DESCRIPTION OF DOWNSTREAM PROCESS......Page 283
B. CLEARANCE OF CELLULAR PROTEINS ACROSS CHROMATOGRAPHY STEPS......Page 287
IV. SCALE-UP CRITERIA USED FOR SCALING UP THE CHROMATOGRAPHY STEPS......Page 288
V. COMPARISON OF CHROMATOGRAPHY STEPS AT SMALL SCALE AND AT PILOT SCALE......Page 290
B. LESS THAN MONOMER (LTM) IN THE PRODUCT......Page 293
D. VIRUS REMOVAL......Page 295
ACKNOWLEDGMENTS......Page 296
REFERENCES......Page 297
I. INTRODUCTION......Page 298
A. EQUIPMENT......Page 300
A. TWENTY-SIX KILOGRAM CAMPAIGN......Page 301
B. ONE HUNDRED SIXTY KILOGRAM CAMPAIGN......Page 306
REFERENCES......Page 309
I. BACKGROUND......Page 311
II. METHOD DEVELOPMENT......Page 312
B. DEVELOPMENT OF PREPARATIVE SEPARATION......Page 314
C. DEVELOPMENT OF CLEANING PROTOCOL FOR RESIN COLUMN......Page 317
D. USE OF ALTERNATIVE FEEDS......Page 318
IV. DEMONSTRATION AT PILOT SCALE......Page 322
V. TRANSFER TO PRODUCTION SCALE......Page 324
I. INTRODUCTION......Page 325
II. PHASES OF PROCESS DESIGN......Page 326
A. RESIN SCREENING......Page 328
B. PROCESS DEVELOPMENT......Page 331
B. CATION-EXCHANGE HPLC......Page 332
A. SP CHROMATOGRAPHIC COLUMN DEVELOPMENT......Page 333
B. Q CHROMATOGRAPHIC COLUMN DEVELOPMENT......Page 340
V. CONCLUSIONS......Page 343
REFERENCES......Page 345