Scaled-Down Models for Purification Processes: Approaches and Applications

Process Validationin Manufacturing of Biopharmaceuticals, Third edition

Volumn , Issue , 2012, Pages 89-140

  Godavarti, Ranga ^a   Petrone, Jon ^b   Robinson, Jeff ^c   Wright, Richard ^a   Kelley, Brian D ^d   Bolton, Glen R ^a  

^a PFIZER INC   (United States)

^b Pall Life Sciences   (United States)

^c Lonza Inc ^*  (United States)

^d GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84963676056     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b12013-9     Document Type: Chapter

References (121)

1. Center for Biologics Evaluation and Research, FDA (Food and Drug Administration). “Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, " 1997.
2. Center for Biologics Evaluation and Research, FDA (Food and Drug Administration). “Guidance for Industry for the Submission of Chemistry, Manufacturing and Controls for a Therapeutic Recombinant DNA-Derived Product or Monoclonal Antibody Product for In Vivo Use, " 1996.
3. Center for Biologics Evaluation and Research, FDA (Food and Drug Administration). “Guideline on General Principles of Process Validation, " 1987.
4. FDA (Food and Drug Administration). “Guidance for Industry, Process Validation: General Principles and Practices (Draft Guidance), " November 2008.
5. Cecchini, D. J. “Application of Design Space for Biopharmaceutical Purification Processes.” In Quality by Design for Biopharmaceuticals: Principles and Case Studies. Edited by A. S. Rathore and R. Mhatre. Hoboken, NJ: John Wiley and Sons, Inc., 2009.
6. Banerjee, A. “Designing in Quality: Approaches to Defining the Design Space for a Monoclonal Antibody Process.” BioPharm Int 23, no. 5 (2010).
7. Kozlowski, S., and P. Swann. “Considerations for Biotechnology Product Quality by Design.” In Quality by Design for Biopharmaceuticals: Principles and Case Studies. Edited by A. S. Rathore and R. Mhatre. Hoboken, NJ: John Wiley and Sons, Inc., 2009.
8. FDA(Food and Drug Administration)/ICH (International Conference on Harmonization). (Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research). “Q8(R2) Pharmaceutical Development, ICH Guidance for Industry, " August 2009.
9. FDA(Food and Drug Administration)/ICH (International Conference on Harmonization). (Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research). “Q10 Pharmaceutical Quality Systems, ICH Guidance for Industry, " May 2007.
10. FDA(Food and Drug Administration)/ICH (International Conference on Harmonization). (Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research). “Q9 Quality Risk Management, ICH Guidance for Industry, " November 2005.
11. CMC Biotech Working Group. “A-Mab: A Case Study in Bioprocess Development.” Technical Report, 2009, http://www.casss.org/associations/9165/files/A-Mab_Case_Study_Version_2-1.pdf.
12. Food and Drug Administration docket number FDA-2008-N-0355. “Submission of Quality Information for Biotechnology Products in the Office of Biotechnology Products; Notice of Pilot Program.” July 2, 2008, http://federalregister.gov/a/E9-22378.
13. International Conference on Harmonization. “Viral Safety of Biotechnology Products Derived from Cell Lines of Human or Animal Origin.” ICH Viral Safety Document, 1998.
14. Sofer, G., and L. E. Little. “Validation: Ensuring the Accuracy of Scaled-Down Chromatography Models.” BioPharm 9, no. 9 (1996): 51-54.
15. Parenteral Drug Association (PDA). “Process Validation of Protein Manufacturing, " Technical Report No. 42, PDA Journal of Pharmaceutical Science and Technology 59, Supplement S-4, (2005).
16. Coffman, J. L., J. F. Kramarczyk, and B. D. Kelley. “High-Throughput Screening of Chromatographic Separations: I. Method Development and Column Modeling.” Biotech Bioeng 100, no. 4 (2008): 605-618.
17. Chhatre, S., and N. J. Titchener-Hooker. “Review: Microscale Methods for High-Throughput Chromatography Development in the Pharmaceutical Industry.” J. Chem Technol Biotechnol 84 (2009): 927-940.
18. Bergander, T., K. Nilsson-Valimaa, K. Oberg, and K. M. Lacki. “High-Throughput Process Development: Determination of Dynamic Binding Capacity Using Microtiter Filter Plates Filled with Chromatography Resin.” Biotechnol Prog 24 (2008): 632-639.
19. Ghose, S., and H. Chase. “Expanded Bed Chromatography of Proteins in Small Diameter Columns. I. Scale-Down and Validation.” Bioseparation 9 (2000): 21-28.
20. Yamamoto, Y., A. Okamoto, and P. Watler. “Effect of Adsor Bent Properties on Zone Spreading in Expanded Bed Chromatography.” Bioseparation 10 (2001): 1-6.
21. Imamoglu, S. “Simulated Moving Bed Chromatography (SMB) for Application in Bioseparation.” Adv Biochem Eng Biotechnol 76 (2002): 211-231.
22. Smith, T. M., E. Wilson, R. G. Scott, J. W. Misczak, J. M. Bodek, and D. W. Zabriskie. “Establishment of Operating Ranges in a Purification Process of a Monoclonal Antibody.” In Validation of Biopharmaceutical Manufacturing Processes. Edited by B. D. Kelley and R. A. Ramelmier. ACS Symposium Series. Washington, DC: American Chemical Society, 1998, 80-92.
23. Yamamoto, S., K. Nakanishi, and R. Maatsuno. Ion Exchange Chromatography of Proteins. New York: Marcel Dekker, 1988.
24. European Medicines Evaluation Agency. “Revised CPMP Guideline on Virus Validation Studies.” CPMP/268/95, 1995.
25. Gagnon, P., and E. Grund. “Large-Scale Process Development for Hydrophobic Interaction Chromatography, Part 4: Controlling Selectivity.” BioPharm 9, no. 5 (1996): 54-64.
26. Barry, A., R. Chojnacki. “Biotechnology Product Validation, Part 8: Chromatography Media and Column Qualification.” BioPharm 7, no. 9 (1994): 43-47.
27. Sofer, G., and L. Hagel. Handbook of Process Chromatography: A Guide to Optimization, Scale-up, and Validation. New York: Academic Press, 1997.
28. Hjorth, R. “Expanded-Bed Adsorption in Industrial Bioprocessing: Recent Developments.” Trends Biotechnol 15, no. 6 (1997): 230-235.
29. Dasari, G., I. Prince, and M. T. W. Hearn. “High-Performance Liquid Chromatography of Amino Acids, Peptides and Proteins. CXXIV Physical Characterization of Fluidized Bed Behavior of Chromatographic Packing Materials.” J. Chromatogr. 631 (1993): 115-124.
30. Thommes, J., M. Halfar, S. Lenz, and M.-R. Kula. “Purification of Monoclonal Antibodies from Whole Hybridoma Fermentation Broth by Fluidized Bed Adsorption.” Biotechnol. Bioeng. 45, no. 3 (1995): 205-211.
31. Nilsson, J., P. Jonasson, E. Samuelsson, S. Stahl, and M. Uhlen. “Integrated Production of Human Insulin and Its C-Peptide.” J. Biotechnol. 48 (1996): 241-250.
32. Wrotnowski, C. “Neose Targets Complex Carbohydrate Products.” Genet. Eng. News 21, (2001).
33. Bornstein, P., and G. Balian. “The Specific Nonenzymatic Cleavage of Bovine Ribonuclease with Hydroxylamine.” J Biol Chem 245 (1970): 4854-4856.
34. Antorini, M., U. Breme, P. Caccia, C. Grassi, S. Lebrun, G. Orsini, G. Taylor, B. Valsasina, E. Marengo, R. Todeschini, C. Andersson, P. Gellerfors, and J. Gustafsson. “Hydroxylamine-Induced Cleavage of the Asparginyl-Glycine Motif in the Production of Recombinant Proteins: The Case of Insulin-Like Growth Factor I.” Protein Expression and Purification 11 (1997): 135-147.
35. Bornstein, P., and G. Balian. “Cleavage at Asn-Gly Bonds with Hydroxylamine.” Methods Enzymol 47 (1977): 132-145.
36. Ladisch, L., and K. Kohlmann. “Recombinant Human Insulin.” Biotechnol. Prog. 8 (1992): 469-478.
37. Veronese, F., and J. M. Harris. “Introduction and Overview of Peptide and Protein Pegylation.” Adv. Drug Delivery Reviews 54 (2002): 453-456.
38. Roberts, M. J., M. D. Bentley, and J. M. Harris. “Chemistry for Peptide and Protein Pegylation.” Adv. Drug Delivery Reviews 54 (2002): 459-476.
39. Glatz, C. E. “Precipitation.” In Separation Processes in Biotechnology. Edited by J. A. Asenjo. New York: Marcel Dekker, 1990, 329-356.
40. Ladish, M. R. “Precipitation, Crystallization, and Extraction.” In Bioseparations Engineering: Principles, Practice, and Economics. Edited by M. R. Ladish. New York: Wiley-Interscience, 2001, 116-151.
41. Rothstein, F. “Differential Precipitation of Proteins: Science and Technology.” In Protein Purification Process Engineering. Edited by R. G. Harrison. New York: Marcel Dekker, 1990, 115-208.
42. Stryker, M. H., M. J. Bertolini, and Y.-L. Hao. “Blood Fractionation: Proteins.” In Advances in Biotechnological Processes, Volume 4. Edited by A. Mizrahi and A. L. van Wezel. New York: Alan R. Liss, 1985, 275-336.
43. Foster, P. R., and J. G. Watt. “The CSVM Fractionation Process.” In Methods of Plasma Protein Fractionation. Edited by J. M. Curling. London: Academic Press, 1980, 17-31.
44. Chang, C. E. “Continuous Fractionation of Human Plasma Proteins by Precipitation from the Suspension of the Recycling Stream.” Biotechnol Bioeng 31 (1900): 841-846.
45. Bos, O. J. M., D. G. J. Sunye, C. E. F. Nieuweboer, F. A. C. van Engelenburg, H. Schuitemaker, and J. Over. “Virus Validation of pH 4-Treated Human Immunoglobulin Products Produced by the Cohn Fractionation Process.” Biologicals 26 (1998): 267-276.
46. Tatterson, G. B. “Process Translation.” In Scaleup and Design of Industrial Mixing Processes. Edited by G. B. Tatterson. New York: McGraw-Hill, 1994, 203-266.
47. Bell, D. J., and P. Dunnill. “Shear Disruption of Soya Protein Precipitate Particles and the Effect of Aging in a Stirred Tank.” Biotechnol Bioeng 24 (1982): 1271-1285.
48. Byrne, E. P., J. J. Fitzpatrick, L. W. Pampel, and N. J. Titchener-Hooker. “Influence of Shear on Particle Size and Fractal Dimension of Whey Protein Precipitates: Implications for Scale-Up and Centrifugal Clarification Efficiency.” Chem Eng Sci 57 (2002): 3767-3779.
49. US Food and Drug Administration. “Guide to Inspections of Viral Clearance Processes for Plasma Derivatives, " http://www.fda.gov/iceci/inspections/inspectionguides/ucm074866.htm.
50. Willkommen, H. “Experimental Experience with Virus Validation Studies.” Dev Biol Stand 88 (1996): 317-831.
51. Biescas, H., M. Gensana, J. Fernandez, P. Ristol, M. Massot, E. Watson, and F. Vericat. “Characterization and Viral Safety Validation Study of a Pasteurized Therapeutic Concentrate of Antithrombin III Obtained through Affinity Chromatography.” Haematologica 83 (1998): 305-311.
52. Chandra, S., J. E. Cavanaugh, C. M. Lin, C. Pierre-Jerome, N. Yerram, R. Weeks, E. Flanigan, and F. Feldman. “Virus Reduction in the Preparation of Intravenous Immune Globulin: In Vitro Experiments.” Transfusion 39 (1999): 249-257.
53. Neal, G., J. Christie, E. Keshavarz-Moore, and P. A. Shamlou. “Ultra Scale-Down Approach for the Prediction of Full-Scale Recovery of Ovine Polyclonal Immunoglobulins Used in the Manufacture of Snake Venom-Specific Fab Fragment.” Biotechnol Bioeng 81 (2003): 149-157.
54. Boychyn, M., W. Doyle, M. Bulmer, J. More, and M. Hoare. Laboratory Scale-Down of Protein Purification Processes Involving Fractional Precipitation and Centrifugal Recovery.” Biotechnol Bioeng 69 (2000): 1-10.
55. Alonso, W. R., S. Trukawinski, M. Savage, R. A. Tenold, and D. J. Hammond. “Viral Inactivation of Intramuscular Immune Serum Globulins.” Biologicals 28 (2000): 5-15.
56. Johnston, A., A. MacGregor, S. Borovec, M. Hattarki, K. Stuckly, D. Anderson, N. H. Goss, A. Oates, and E. Uren. “Inactivation and Clearance of Viruses during the Manufacture of High Purity Factor IX.” Biologicals 28 (2000): 129-136.
57. Dichtelmuller, H., D. Rudnick, B. Breuer, and K. H. Ganshirt. “Validation of Virus Inactivation and Removal for the Manufacturing Procedure of Two Immunoglobulins and a 5% Serum Protein Solution Treated with Beta-Propiolactone.” Biologicals 21 (1993): 259-268.
58. Josic, D., P. Schulz, L. Biesert, L. Hoffer, H. Schwinn, M. Kordis-Krapez, and A. Strancar. “Issues in the Development of Medical Products Based on Human Plasma.” J. Chrom B 694 (1997): 253-269.
59. Minor, P. “Meeting on the Acceptance Criteria for Virus Validation Studies.” Biologicals 23 (1995): 107-110.
60. Meltzer, T. H., and M. W. Jornitz. Filtration in the Biopharmaceutical Industry. New York: Marcel Dekker, 1998.
61. Zeman, L. J., and A. L. Zydney. Microfiltration and Ultrafiltration: Principles and Applications. New York: Marcel Dekker, 1996.
62. Mir, L., S. L. Michaels, V. Goel, and R. Kaiser. “Crossflow Microfiltration: Applications, Design, and Cost.” In Membrane Handbook. Edited by W. S. W. Ho and K. K. Sirkar. New York: Van Nostrand Reinhold, 1992, 571-594.
63. Goel, V., M. A. Accomazzo, A. J. DiLeo, P. Meier, A. Pitt, M. Pluskal, and R. Kaiser. “Dead-End Microfiltration: Applications, Design, and Cost.” In Membrane Handbook. Edited by W. S. W. Ho and K. K. Sirkar. New York: Van Nostrand Reinhold, 1992, 506-569.
64. Li, H., A. G. Fane, and H. G. L. Coster. “Vigneswaran: An Assessment of Depolarization Models of Crossflow Microfiltration by Direct Observation through the Membrane.” J. Membrane Sci 172 (2000): 135-147.
65. Wolber, P., M. Dosmer, and J. Banks. “Cell Harvesting Scale-Up: Parallel-Leaf Cross-Flow Microfiltration Methods.” BioPharm Manufacturing 1, no. 6 (1988): 38-45.
66. van Reis, R., L. C. Leonard, C. C. Hsu, and S. E. Builder. “Industrial Scale Harvest of Proteins from Mammalian Cell Culture by Tangential Flow Filtration.” Biotechnol Bioeng 36 (1991): 413-422.
67. van Reis, R., S. Gadam, L. N. Frautschy, S. E. Orlando, E. M. Goodrich, S. Saksena, R. Kuriyel, C. M. Simpson, S. Pearl, and A. L. Zydney. “High Performance Tangential Flow Filtration.” Biotechnol Bioeng 56 (1997): 71-82.
68. Cheryan, M. Ultrafiltration Handbook. Lancaster, PA: Technomic Publishing, 1986.
69. van Reis, R., and A. L. Zydney. “Protein Ultrafiltration.” In Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation. Edited by M. C. Flickinger. New York: John Wiley and Sons, 1999, 2197-2214.
70. wall Ultrafiltration Process Control.” J Membrane Sci 130 (1997): 123-140.
71. Brose, D., M. Dosmar, S. Cates, and F. Hutchison. “Studies on the Scale-Up of Crossflow Filtration Devices.” PDA J Pharm Sci Technol 50, no. 4 (1996): 252-260.
72. van Reis, R., E. M. Goodrich, C. L. Yson, L. N. Frautschy, S. Dzengeleski, and H. Lutz. “Linear Scale Ultrafiltration.” Biotechnol Bioeng 55, no. 5 (1997): 737-746.
73. Meireles, M., P. Aimar, and V. Sanchez. “Albumin Denaturation during Ultrafiltration: Effects of Operating Conditions and Consequences on Membrane Fouling.” Biotechnol Bioeng 38 (1991): 528-534.
74. Maa, Y. F., and C. C. Hsu. “Protein Denaturation by Combined Effect of Shear and Air-Liquid Interface.” Biotechnol Bioeng 54 (1997): 503-512.
75. Kim, K. J., V. Chen, and A. G. Fane. “Some Factors Determining Protein Aggregation during Ultrafiltration.” Biotechnol Bioeng 42 (1993): 260-265.
76. Frampton, G. A. “Evaluating the Performance of Industrial Centrifuges.” Chem Eng Prog, August 1963, 402-412.
77. Kempken, R., A. Preissmann, and W. Berthold. “Assessment of a Disc Stack Centrifuge for Use in Mammalian Cell Separation.” Biotechnol Bioeng 46 (1995): 132-138.
78. Mannweiler, K., and M. Hoare. “The Scale Down of an Industrial Disc Stack Centrifuge.” Bioproc Eng 8 (1992): 19-25.
79. Ambler, C. M. “The Evaluation of Centrifuge Performance.” Chem Eng Prog 48 (1952): 150-158.
80. Ambler, C. M. “The theory of scaling up laboratory data for the sedimentation type centrifuge.” J Biochem Microbiol Tech Eng 1, no. 2 (1959): 185-205.
81. Maybury, J. P., M. Hoare, and P. Dunnil. “The Use of Laboratory Centrifugation Studies to Predict Performance of Industrial Machines: Studies of Shear-Insensitive and Shear-Sensitive Materials.” Biotechnol Bioeng 67, no. 3 (2000): 265-273.
82. Trowbridge, M. E. “Problems in the Scaling-Up of Centrifugal Separation Equipment.” Chem Eng, August 1962, A73-A87.
83. Boychyn, M., S. S. S. Yim, E. M. Bulmer, J. More, D. G. Bracewell, and E. M. Hoare. “Performance Prediction of Industrial Centrifuges Using Scale-Down Models.” Bioprocess Biosyst Eng 26 (2004): 385-391.
84. Berrill, A., S. V. Ho, and D. G. Bracewell. “Ultra Scale-Down to Define and Improve the Relationship between Flocculation and Disc-Stack Centrifugation.” Biotechnol Prog 24 (2008): 426-431.
85. Maybury, J. P., K. Mannweiler, N. J. Titchener-Hooker, M. Hoare, and P. Dunnil. “The Performance of a Scaled-Down Industrial Disc Stack Centrifuge with a Reduced Feed Material Requirement.” Bioproc Eng 18 (1998): 191-199.
86. st Century: Part 3a Plasma and Plasma Products (Heat and Solvent/Detergent Treatments).” BioPharm 15, no. 9 (2002): 28-42.
87. st Century: Part 3b Plasma and Plasma Products (Treatments Other Than Heat or Solvent/Detergent).” BioPharm 15, no. 10 (2002): 42-49.
88. st Century: Part 4 Culture Media, Biotechnology Products, and Vaccines.” BioPharm Int 16, no. 1 (2003): 50-57.
89. Fisher, G., W. K. Hoots, and C. Abrams. “Viral Reduction Techniques: Types and Purpose.” Transfusion Medicine Rev 15, Supplement 1 (2001): 27-39.
90. Roberts, P. “Virus Safety of Plasma Products.” Reviews Med Virol 6 (1996): 25-38.
91. Charm, S. E., S. Landau, B. Williams, B. Horowitz, A. M. Prince, and D. Pascual. “High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma.” Vox Sang 62 (1992): 12-20.
92. Walter, J. K., F. Nothelfer, and W. Werz. “Validation of Viral Safety for Pharmaceutical Proteins.” In Bioseparation and Bioprocessing, Vol 1. Edited by G. Subramanian. Weinheim: Wiley-VCH, 1998, 465-496.
93. Chandra, S., A. Groener, and F. Feldman. “Effectiveness of Alternative Treatments for Reducing Potential Viral Contaminants from Plasma-Derived Products.” Thrombosis Res 105 (2002): 391-400.
94. Tatterson, G. B. “Basic Processing Concepts.” In Scaleup and Design of Industrial Mixing Processes. New York: McGraw-Hill, 1994, 1-52.
95. Committee for Proprietary Medicinal Products, European Medicines Evaluation Agency. “Note of Guidance on Plasma-Derived Medicinal Products.” CMPM/BWP/269/95 Rev 3. London: European Agency for the Evaluation of Medicinal Products, 2001.
96. Roberts, P. L., and C. Dunkerley. “Effect of Manufacturing Process Parameters on Virus Inactivation by Solvent-Detergent Treatment in a High-Purity Factor IX Concentrate.” Vox Sang 84 (2003): 170-175.
97. Seitz, H., J. Blumel, I. Schmidt, H. Willkommen, and J. Lower. “Comparable Virus Inactivation by Bovine or Vegetable Derived Tween 80 during Solvent/Detergent Treatment.” Biologicals 30 (2002): 197-205.
98. Morfeld, F., R. Schutz, D. Josic, and H. Schwinn. “Manufacturing and Down Scaling Process for a Virus-Inactivated Pooled Human Plasma.” Pharm Ind 58 (1996): 433-435.
99. Blumel, J., I. Schmidt, H. Willkommen, and J. Lower. “Inactivation of Parvovirus B19 during Pasteurization of Human Serum Albumin.” Transfusion 42 (2002):1011-1018.
100. Adcock, W. L., A. MacGregor, J. R. Davies, M. Hattarki, D. A. Anderson, and N. H. Goss. “Chromatographic Removal and Heat Inactivation of Hepatitis A Virus during Manufacture of Human Albumin.” Biotechnol Appl Biochem 28 (1998): 85-94.
101. Lieber, M. M., R. E. Benveniste, D. M. Livingston, and G. J. Todaro. “Mammalian Cells in Cell Culture Frequently Release Type C Viruses.” Science 182 (1973): 56-59.
102. Levy, J., H. Lee, R. Kawahata, and L. Spitler. “Purification of Monoclonal Antibodies from Mouse Ascites Eliminates Contaminating Infectious Mouse Type C Viruses and Nucleic Acids.” Clin Exp Immunology 56 (1984): 114-120.
103. Levy, R. V., M. W. Phillips, and H. Lutz. “Filtration and Removal of Viruses from Biopharmaceuticals.” In Filtration in the Biopharmaceutical Industry. Edited by T. H. Meltzer and M. W. Jornitz. New York: Marcel Dekker, 1998, 619-646.
104. Kelley, B. D., and J. T. Petrone. “Virus Removal by Tangential Flow Filtration for Protein Therapeutics.” In Membrane Separations in Biotechnology. Edited by W. K. Wang. New York: Marcel Dekker, 2001, 351-396.
105. Huang, P. Y., and J. Peterson. “Scaleup and Virus Clearance Studies on Viral Filtration in Monoclonal Antibody Manufacture.” In Membrane Separations in Biotechnology. Edited by W. K. Wang. New York: Marcel Dekker, 2001, 327-350.
106. Saksena, S., and A. L. Zydney. “Effect of Solution pH and Ionic Strength on the Separation of Albumin from Immunoglobulins by Selective Filtration.” Biotechnol Bioeng 43 (1994): 960-968.
107. Bil’dyukevich, A. V., E. G. Ostrovskii, and F. N. Kaputskii. “Ultrafiltration of Model Solutions of High-Molecular-Weight Compounds. Influence of the Ionic Strength on the Ultrafiltration of Protein Solutions.” Colloid Journal of the USSR 51 (1989): 300-303.
108. van Holten, R. W., G. J. Quinton, and G. E. Oulundsen. “Viral Clearance Process.” US Patent #6, 096, 872, 2000.
109. Box, G. E. P., W. G. Hunter, and J. S. Hunter. Statistics for Experimenters. New York: John Wiley and Sons, 1978, 31-38 and 73.
110. Seely, R. J., L. Munyakazi, J. Haury, H. Simmerman, W. H. Rushing, and T. F. Curry. “Demonstrating the Consistency of Small Datasets.” BioPharm Int’l 16, no. 5 (2003): 36-58.
111. Morrica, A., C. Nardini, A. Falbo, A. C. Bailey, and E. Bucci. “Manufacturing Process of Anti-thrombin III Concentrate: Viral Safety Studies and Effect of Column Re-use on Viral Clearance.” Biologicals 31 (2003): 165-173.
112. Leonard, M. W., L. Sefton, R. Costigan, L. Shi, B. Hubbard, D. Bonam, B. D. Kelley, B. Foster, and T. Charlebois. “Validation of Recombinant Coagulation Factor IX Purification Process for Removal of Host Cell DNA.” In Validation of Biopharmaceutical Manufacturing Processes. Edited by B. D. Kelley and R. A. Ramelmier. ACS Symposium Series. Washington, DC: American Chemical Society, 1998, 55-68.
113. Adner, N., and G. Sofer. “Biotechnology Product Validation, Part 3: Chromatography Cleaning Validation.” BioPharm 7, no. 3 (1994): 44-48.
114. Shi, L., B. D. Kelley, D. Bonam, and B. Hubbard. “Experimental Design for Validation of Chromatographic Process Limits.” BioPharm Meeting, San Francisco, 1997.
115. Kelley, B. D. “Establishing Process Robustness Using Designed Experiments.” In Biopharmaceutical Process Validation. Edited by G. Sofer and D. Zabriskie. New York: Marcel Dekker, 2000, 29-59.
116. Breece, T., E. Gilkerson, and C. Schmelzer. “Validation of Large-Scale Chromatographic Process, Part 1. Case Study of Neuleze Capture on Macroprep High-S.” BioPharm 15, no. 5 (2002): 16-20.
117. O’Leary, R. M., D. Feuerhelm, D. Peers, Y. Xu, and G. Blank. “Determining the Useful Lifetime of Chromatographic Resins. Prospective Small-Scale Studies.” BioPharm 14, no. 9 (2001): 10-18.
118. Nigam, S., G. Ruezinsky, and J. Dugger. “Reuse Validation of an Anion Exchange Chromatography Step for Purification of Clinical Grade Ciliary Neurotropic Factor.” In Validation of Biopharmaceutical Manufacturing Processes. Edited by B. D. Kelley and R. A. Ramelmier. ACS Symposium Series. Washington, DC: American Chemical Society, 1998, 125-143.
119. Seely, R., H. Wright, H. Fry, S. Rudge, and G. Slaff. “Biotechnology Product Validation, Part 7: Validation of Chromatography Resin Useful Life.” BioPharm 7, no. 7 (1994): 41-48.
120. Moran, E. B., S. T. McGowan, J. M. McGuire, J. E. Frankland, I. A. Oyebade, W. Waller, L. C. Archer, L. O. Morris, J. Pandya, S. R. Nathan, L. Smith, M. L. Cadette, and J. T. Michalowski. “A Systematic Approach to the Validation of Process Control Parameters for Monoclonal Antibody Production in Fed-Batch Culture of a Murine Myeloma.” Biotechnology and Bioengineering 69, no. 3 (2000): 242-255.
121. Gardner, A. R., and T. M. Smith. “Identification and Establishment of Operating Ranges of Critical Process Variables.” In Biopharmaceutical Process Validation. Edited by G. Sofer and D. Zabriskie. New York: Marcel Dekker, 2000, 61-76.