Pharmaceutical water : system design, operation, and validation

Contents......Page 3
Preface......Page 9
Acknowledgments......Page 11
Definition of Pharmaceutical Waters......Page 12
Chemical Specifications......Page 13
Bacteria Action and Alert Limits......Page 18
Added Substances......Page 23
Foreign Substances and Impurities......Page 25
References......Page 26
Particulate Matter......Page 27
Ionic Material......Page 28
Dissolved Gases: Nonreactive......Page 34
Dissolved Gases: Reactive......Page 36
Microorganisms......Page 39
Bacterial Endotoxins......Page 42
Organic Material......Page 43
Colloids......Page 44
Residual Disinfectant......Page 46
Disinfection By-Products......Page 49
References......Page 50
Appendix: Character of Water Supplies......Page 54
3. Pretreatment Techniques......Page 57
Chemical Injection Systems......Page 58
Injection of Reducing Agent for Removal of Residual Disinfectant Agent......Page 63
Sodium Hydroxide Injection in Systems Using Reverse Osmosis......Page 65
Thermal Blending Systems......Page 67
Heat Exchangers......Page 71
Particulate Removal Filters......Page 79
Activated Carbon Units......Page 93
Water Softening Units......Page 107
Organic Scavenging Resins......Page 118
In-Line Ultraviolet Units......Page 122
Recirculation and Repressurization Pumps......Page 128
Cartridge Filtration......Page 134
References......Page 138
Description and Classification of Ion Exchange Resins......Page 141
Basic Theory......Page 145
Water Softening......Page 150
Conventional, Cocurrent-Regenerated Two-Bed Deionization Systems......Page 160
Countercurrent-Regenerated Deionization Units Fixed Beds......Page 173
Cation Polishers......Page 178
Mixed Bed Deionization Units......Page 179
References......Page 186
5. Primary Ion Removal Techniques—Reverse Osmosis......Page 188
Theory and Application......Page 189
Design Considerations......Page 218
Operating and Maintenance Considerations......Page 233
References......Page 238
Electrodialysis and Electrodialysis Reversal......Page 241
Continuous Electrodeionization......Page 267
References......Page 274
Theory and Application......Page 276
Design Considerations......Page 283
Operating and Maintenance Considerations......Page 324
References......Page 330
Theory and Application......Page 331
Design Considerations......Page 338
Operating and Maintenance Considerations......Page 372
References......Page 375
Distribution Pumps......Page 377
In-Line Ultraviolet Units......Page 386
Polishing Ion Removal......Page 393
Final Membrane Filtration......Page 403
Ultrafiltration......Page 414
Ozone Treatment......Page 429
References......Page 438
10. Distribution Systems—Design, Installation, and Material Selection......Page 441
Theory and Application......Page 442
Design Considerations......Page 451
Operating and Maintenance Considerations......Page 485
References......Page 493
Overview......Page 495
Symbols......Page 496
Process and Instrumentation Diagram......Page 503
Control Functions for Pharmaceutical Water Purification Systems......Page 512
USP Purified Water and Water for Injection Conductivity Measurement......Page 516
Total Organic Carbon Analyzers......Page 518
References......Page 523
12. System Design and Specification Guidelines......Page 524
General Discussion......Page 525
Specification Example: Hot Water Sanitizable, Activated Carbon Unit......Page 532
Specification Example: Stainless Steel Tubing Installation and Associated Support Documentation......Page 535
Appendix A: Section 102: Hot Water Sanitizable, Activated Carbon Unit......Page 540
Appendix B: Section 120: Purified Water Stainless Steel Distribution Tubing and Fittings......Page 554
13. System Validation......Page 566
General Discussion......Page 568
Installation Qualification Protocol: USP Water for Injection Storage Tank with Accessories......Page 584
Operational Qualification Protocol: USP Water for Injection Storage Tank with Accessories......Page 589
Performance Qualification Protocol: USP Water for Injection Storage Tank with Accessories......Page 593
References......Page 598
Appendix A: Installation Qualification for an USP Water for Injection Storage Tank......Page 600
Appendix B: Operational Qualification for an USP Water for Injection Storage Tank......Page 623
Appendix C: Performance Qualification for an USP Water for Injection Storage Tank......Page 636
A......Page 655
B......Page 656
C......Page 658
D......Page 661
E......Page 663
F......Page 664
H......Page 665
I......Page 666
M......Page 667
O......Page 669
P......Page 670
Q......Page 673
R......Page 674
S......Page 676
T......Page 680
U......Page 681
V......Page 682
W......Page 683
Z......Page 684