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Chapter 13 : Manufacture of Mammalian Cell Biopharmaceuticals

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Abstract:

This chapter presents a review on important aspects of the manufacturing of biopharmaceuticals in mammalian systems. These include recovery, purification, formulation, fill and finish, bioanalytics, and current Good Manufacturing Practices (cGMP). Purification process optimization must examine the operation of units in concert with one another, and the ultimate goal is to make as much purified product as possible by the cheapest, quickest, most reproducible, and most robust and efficient route. Viral contamination is a risk to all biopharmaceutical products (including MAbs) derived from cell lines of human or animal origin. The goals of cGMP can be summarized as: protect the product from contamination; prevent mix-ups; know what you are to do before you do it; document what really happens; strive for consistency and control; have an independent group make the final decisions; and solve problems, learn from mistakes, monitor, and continuously improve. MAb manufacturers prepare written validation plans or protocols that specify procedures, tests, and necessary data and analyses. In the manufacture under cGMP guidelines, raw materials (RMs) need to be characterized and released to ensure that they meet predefined specifications on their quality. Manufacture of biopharmaceutical is governed by various cGMP regulations, requiring validation of process, qualification/release of all raw materials (RMs), and thorough testing/release of cell banks and products to ensure safety and potency. Costs are high for production using mammalian cell systems due to expensive facilities, equipment, RMs, testing, validation, etc. Alternative operation approaches are emerging, including incorporation of more single-use devices and outsourcing.

Citation: Zhang J. 2010. Manufacture of Mammalian Cell Biopharmaceuticals, p 179-195. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch13

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High-Performance Liquid Chromatography
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References

/content/book/10.1128/9781555816827.ch13
1. Akers, M. 2006. Special challenges in production of bio-pharmaceutical dosage forms. BioProcess Int. 4:3643.
2. Andya, J. D.,, C. C. Hsu, and, S. J. Shire. 2003. Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations. AAPS PharmSci. 5:E10.
3. Anicetti, V. 2009. Biopharmaceutical processes: a glance into the 21st century. BioProcess Int. 7:S4–S11.
4. Artelis sA and selexis sA. 2008. Artelis and Selexis announces 31 g/L yields in multiple perfusion harvests. BioPharm. Bull. sept.(Online.) http://biopharminternational.findpharma.com/biopharm/issue/issueDetail.
5. Arunakumari, A. 2009. Implementing cost reduction strategies for HuMab manufacturing processes. BioProcess Int. 7:S48S54.
6. Arunakumari, A.,, J. M. Wang, and, G. Ferreira. 2007. Alternative to Protein A: improved downstream process design for human monoclonal antibody production. BioPharm Int. 20:S36S40.
7. Arunakumari, A.,, J. M. Wang, and, G. Ferreira. 2007. Improved downstream process design for human monoclonal antibody production. BioPharm Int. 20:S6S10.
8. Arunakumari, A.,, J. M. Wang, and, G. Ferreira. 2009. Advances in non-Protein A purification processes for human monoclonal antibodies. BioPharm Int. 22:S22S26.
9. Balasubramanian, U.,, P. Salmon,, D. Robinson, and, J. Zhang. 2006. Characterization and release of raw materials used in upstream processes for production of monoclonal antibodies by mammalian cell culture. BioProcess. J. 5:713.
10. Bansal, S. K.,, T. Layloff,, E. D. Bush,, M. Hamilton,, E. A. Hankinson,, J. S. Landy,, S. Lowes,, M. M. Nasr,, P. A. St. Jean, and, V. P. Shah. 2004. Qualification of analytical instruments for use in the pharmaceutical industry: a scientific approach. AAPS PharmSci. 5:E22.
11. Beck, A.,, E. Wagner-Rousset,, M. C. Bussat,, M. Lokteff,, C. Klinguer-Hamour,, J. F. Haeuw,, L. Goetsch,, T. Wurch,, A. van Dorsselaer, and, N. Corvaia. 2008. Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fcfusion proteins. Curr. Pharm. Biotechnol. 9:482501.
12. BioPharm International. 2004. Guide to formulation, fill, and finish. BioPharm Int. 17:S1S42.
13. Birch, J. R.,, J. Bonnerjea, and, S. Flatman. 1995. The production of monoclonal antibodies, p. 231–265. In J. R. Birch and, E. S. Lennox (ed.), Monoclonal Antibodies: Principles and Applications. John Wiley & Sons, Inc., Hoboken, NJ.
14. Boyd, P. N.,, A. C. Lines, and, A. K. Patel. 1995. The effect of the removal of sialic acid, galactose, and total carbohydrate on the functional activity of CAMPATH-1H. Mol. Immunol. 32:13111318.
15. Brorson, K.,, S. Krejci,, K. Lee,, E. Hamilton,, K. Stein, and, Y. Xu, 2003. Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins. Biotechnol. Bioeng. 82:321329.
16. Buchacher, A., and , G. Iberer. 2006. Purification of intravenous immunoglobulin G from human plasma—aspects of yield and virus safety. Biotechnol. J. 2:148163.
17. Cappia, J. M., and , N. B. T. Holman. 2004. Integrating single-use disposable processes into critical aseptic processing operations. BioProcess Int. 2:S56S63.
18. Cardona, M., and , B. Allen. 2006. Incorporating single-use systems in biopharmaceutical manufacturing. BioProcess Int. 4:S10S14.
19. Carpenter, J. F.,, B. S. Chang,, W. Garzon-Rodriguez, and, T. W. Randolph. 2002. Rational design of stable lyophilized protein formulations: theory and practice, p. 109–133. In J. F. Carpenter and, M. C. Manning (ed.), Rational Design of Stable Protein Formulations: Theory and Practice. Springer, Berlin, Germany.
20. Carpenter, J. F.,, M. J. Pikal,, B. S. Chang, and, T. W. Randolph. 1997. Rational design of stable lyophilized protein formulations: some practical advice. Pharm. Res. 14:965975.
21. Carter, J., and , H. Lutz. 2003. Validation of virus filtration—ensuring regulatory compliance. BioProcess Int. 1:5262.
22. Chang, L.,, D. Shepherd,, J. Sun,, D. Ouellette,, K. L. Grant,, X. Tang, and, M. J. Pikal. 2005. Mechanism of protein stabilization by sugars during freeze-drying and storage: native structure preservation, specific interaction, and/or immobilization in a glassy matrix? J. Pharm. Sci. 94:14271444.
23. Chen, B.,, G. Zapata, and, S. M. Chamow. 2003. Strategies for rapid development of liquid and lyophilized antibody formulations. BioProcess Int. 2:4655.
24. Clutterbuck, A. 2008. Integrating and streamlining biopharm purification processes. Innovations Pharm. Technol. October:4246.
25. Committee for Human Medicinal Products/Biotechnology Working Party. 2001. Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses. CHMP/BWP/268/95. EMEA, London, United Kingdom.
26. Curling, J., and , U. Gottschalk. 2007. Process chromatography: five decades of innovation. BioPharm Int. 20:7093.
27. Daugherty, A., and , R. J. Mrsny. 2006. Formulation and delivery issues for monoclonal antibody therapeutics. Adv. Drug Deliv. Rev. 58:686706.
28. Davies, J. 2009. A purification platform for the production of MAbs from fermentors with titers of 5 g/L and beyond. BioPharm Int. 22:S28S31.
29. Defrancq, L.,, N. Callewaert,, J. Zhu,, W. Laroy, and, R. Contreras. 2004. High-throughput analysis of the N-glycans of NS0 cell-secreted antibodies. BioProcess Int. 2:6068.
30. DePalma, A. 2008. Reducing downstream purification cost. Genet. Eng. Biotechnol. News 28(13).
31. DePaz, R. A.,, C. C. Barnett,, D. A. Dale,, J. F. Carpenter,, A. L. Gaertner, and, T. W. Randolph. 2000. The excluding effect of sucrose on a protein chemical degradation pathway: methionine oxidation in subtilisin. Arch. Biochem. Biophys. 384:123132.
32. Diblasi, K.,, M. W. Jornitz,, U. Gottschalk, and, P. M. Priebe. 2007. Disposable biopharmaceutical processes—myth or reality? BioPharm Int. 20:S19S24.
33. Dinowitz, M.,, Y. S. Lie,, M. A. Low,, R. Lazar,, C. Fautz,, B. Potts,, J. Sernatinger, and, K. Anderson. 1992. Recent studies on retrovirus-like particles in Chinese hamster ovary cells. Dev. Biol. Stand. 76:201207.
34. Dominguez, C. A.,, E. Rivera,, C. Escaboar, and, J. Weidner. 2008. Improving tangential flow filtration yield. BioPharm Int. 21:4259.
35. Dorsey, N.,, J. Eschrich, and, G. Cyr. 1997. The role of charge in the retention of DNA by charged cellulose based depth filters. BioPharm Int. 10:4649.
36. Dougherty, J.,, R. Mhatre, and, S. Moore. 2003. Using peptide maps as identity and purity tests for lot release testing of recombinant therapeutic proteins. BioPharm Int. 16:5458.
37. Drickamer, K. 1991. Clearing up glycoprotein hormones. Cell 67:10291932.
38. Dutton, G. 2008. Downstream bottlenecks: are they myth or reality? Genet. Eng. Biotechnol. News 28(8).
39. Eppink, M. H. M.,, R. Schreurs,, A. Gusen, and, K. Verhoeven. 2009. Platform technology for developing purification processes. BioPharm Int. 22:S32S36.
40. European commission. 2009. EudraLex. The rules governing medicinal products in the European Union, vol. 4. Good manufacturing practice (GMP) guidelines, annex 8. Sampling of starting and packaging materials. European Commission, Brussels, Belgium. (Online.) http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-4/pdfs-en/anx08en.pdf.
41. European Medicines Evaluation Agency. 2001. Note for guidance on minimizing the risk of transmitting animal spongiform encephalopathies via human and veterinary medicinal products. EMEA/410/01, Rev. 2. EMEA, London, United Kingdom.
42. European Medicines Evaluation Agency. 2001. Guideline on virus safety evaluation of biotechnological investigational medicinal products. EMEA/CHMP/BWP/398498/2005. EMEA, London, United Kingdom.
43. Fahrner, R. L.,, H. L. Knudsen,, C. D. Basey,, W. Galan,, D. Feuerheim,, M. Vanderlaan, and, G. S. Blank. 2001. Industrial purification of pharmaceutical antibodies: development, operation, and validation of chromatography processes. Genet. Eng. Biotechnol. Rev. 18:301327.
44. Farid, S. S. 2008. Economic drivers and trade-offs in antibody purification processes. BioPharm. Int. 21:S37S42.
45. Farid, S. S.,, J. Washbrook, and , N. J. Titchener-Hooker. 2005. Decision-support tool for assessing biomanufacturing strategies under uncertainty: stainless steel versus disposable equipment for clinical trial material preparation. Biotechnol. Prog. 21:486497.
46. Farshid, M.,, R. E. Taffs,, D. Scott,, D. M. Asher, and, K. Brorson. 2005. The clearance of viruses and transmissible spongiform encephalopathy agents from biologicals. Curr. Opin. Biotechnol. 16:561567.
47. Federal Register. 1995. Interim definition and elimination of lot-by-lot release for well-characterized therapeutic recombinant DNA-derived and monoclonal antibody biotechnology products. Fed. Regist. 60: 63048.
48. Federal Register. 1996. Well-characterized biotechnology products: elimination of establishment license application. Fed. Regist. 61: 2733.
49. Fetterolf, D. M. 2007. Developing a sound process validation strategy. BioPharm Int. 20:3846.
50. Food and Drug Administration. 1987. Guideline on general principles of process validation. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124720.htm
51. Food and Drug Administration. 1993. Points to consider in the characterization of cell lines used for biological products. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Biolog-icsBloodVaccines/GuidanceComplianceRegulatoryIn-formation/OtherRecommendationsforManufacturers/UCM062745.pdf
52. Food and Drug Administration. 1995. FDA guidance document concerning use of pilot manufacturing facilities for the development and manufacture of biological products. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/General/UCM168111.pdf
53. Food and Drug Administration. 1987. Points to consider in the manufacture and testing of monoclonal antibody products for human use. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/OtherRecommendationsforManufacturers/UCM153182.pdf
54. Food and Drug Administration. 1998. Guidance for industry: Q5A viral safety evaluation of biotechnological products derived from cell lines of human or animal origin (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129101.pdf
55. Food and Drug Administration. 1999. Guidance on specifications: Q6B test procedures and acceptance criteria for biotechnological/biological products (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129100.pdf
56. Food and Drug Administration. 2001. Guidance for industry: analytical procedures and methods validation. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory-Information/Guidances/ucm122858.pdf
57. Food and Drug Administration. 2001. Guidance for industry: bioanalytical method validation. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory-Information/Guidances/UCM070107.pdf
58. Food and Drug Administration. 2001. Guidance for industry: Q7A good manufacturing practice for active pharmaceutical ingredients (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129098.pdf
59. Food and Drug Administration. 2003. Guidance for industry: Q1A(R2) stability testing of new drug substances and products (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm128204.pdf
60. Food and Drug Administration. 2004. Guidance for industry: sterile drug products produced by aseptic processing—current good manufacturing practice. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory-Information/Guidances/ucm070342.pdf
61. Food and Drug Administration. 2005. Guidance for industry: Q2(R1) validation of analytical procedures: test and methodology (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/down-loads/RegulatoryInformation/Guidances/UCM128048.pdf; http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM128049.pdf
62. Food and Drug Administration. 2005. Guidance for industry: Q5E comparability of biotechnological/biological products subject to changes in their manufacturing process (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm128076.pdf
63. Food and Drug Administration. 2006. Guidance for industry: Q9 quality risk management (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory-Information/Guidances/ucm073511.pdf
64. Food and Drug Administration. 2008. Current good manufacturing practices for finished pharmaceuticals (21 CFR, Part 211). Food and Drug Administration, Rockville, MD. (Online.) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211&showFR=1
65. Food and Drug Administration. 2008. Guidance for industry: cGMP for phase 1 investigational drugs. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070273.pdf
66. Food and Drug Administration. 2008. Guidance for industry: process validation: general principles and practices. Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/Drugs/GuidanceCompliance-RegulatoryInformation/Guidances/UCM070336.pdf
67. Food and Drug Administration. 2007. Guidance for industry: Q10 pharmaceutical quality system (ICH). Food and Drug Administration, Rockville, MD. (Online.) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm128031.pdf
68. Frankin, S. 2003. Removal of aggregate from an IgG4 product using CHT ceramic hydroxyapatite. BioProcess Int. 1:5051.
69. Fraud, N. 2008. Membrane chromatography: an alternative to polishing column chromatography. BioProcess. J. 7:3448.
70. Ganderton, D. 1991. The development of peptide and protein pharmaceuticals, p. 211–277. In R. C. Hider and, D. Barlow (ed.), Polypeptide and Protein Drugs: Production, Characterization, and Formulation. Ellis Horwood Ltd., Chichester, United Kingdom.
71. Giovannoni, L.,, M. Ventani, and, U. Gottschalk. 2008. Antibody purification using membrane adsorbers. BioPharm Int. 21:4852.
72. Glynn, J.,, T. Hagerty,, T. Pabst,, G. Annathur,, K. Thomas,, P. Johnson,, N. Ramasubramanyan, and, P. Mensah. 2009. The development and application of a monoclonal antibody purification platform. BioPharm Int. 22:S16S20.
73. Goolcharran, C.,, J. L. Cleland,, R. Keck,, A. J. Jones, and, R. T. Borchardt. 2000. Comparison of the rates of deamidation, diketopiperazine formulation and oxidation in recombinant human vascular endothelial growth factor and model peptides. AAPS PharmSci. 2:E5.
74. Gottschalk, U. 2007. The renaissance of protein purification. BioPharm Int. 20:S41S42.
75. Gottschalk, U., and , S. Fishcherfruehholz. 2004. A cutting edge process technology at the threshold. BioProcess Int. 2:5665.
76. Guhan, J.,, Y. F. Li,, J. A. Moore, and, S. M. Cramer. 1995. Ionexchange displacement chromatography of proteins: dendritic polymers as novel displacers. J. Chromatogr. A 702:143155.
77. Imensek, M. 2003. Sterile fill facilities: problems and resolutions. Biopharm Int. 16:4454.
78. Immelmann, A.,, K. Kellings,, O. Stamm, and, K. Tarrach. 2005. Validation and quality procedures for virus and prion removal in biopharmaceuticals. BioProcess Int. 3:S26S31.
79. International society for Pharmaceutical Engineering. 2001. GAMP 4 to GAMP 5 summary. International Society for Pharmaceutical Engineering, Tampa, FL. (Online.) http://www.ispe.org/galleries/publications-files/GAMP_4_ to_GAMP_5_Summary.pdf.
80. Iyer, H.,, F. Henderson,, E. Cunningham,, J. Welbb,, J. Hanson,, C. Bork, and, L. Conley. 2002. Considerations during development of a Protein A-based antibody purification process. BioPharm Int. 15:1420.
81. Jacob, L. R., and , M. Frech. 2004. Scale up of antibody purification: from laboratory scale to production, p. 101–132. In G. Subramanian (ed.), Antibodies, vol. 1. Production and Purification. Kluwer Academic/Plenum Publishers, New York, NY.
82. Jacobsen, M, and, C. Sandstrom. 2006. An approach to optimizing large-scale cell harvest. BioProcess Int. 4:2835.
83. Jefferis, R. 2005. Glycosylation of recombinant antibody therapeutics. Biotechnol. Prog. 21:1116.
84. Jorgensen, K., and , T. Naes. 2004. A design and analysis strategy for situations with uncontrolled raw material variation. J. Chemometrics 18:4552.
85. Kadarusman, J.,, R. Bhatia,, J. McLaughlin, and, W. R. Lin. 2005. Growing cholesterol-dependent NS0 myeloma cell line in the Wave bioreactor system: overcoming cholesterol-polymer interaction by using pretreated polymer or inert fluorinated ethylene propylene. Biotechnol. Prog. 21:13411346.
86. Kamarck, M. E. 2006. Building biomanufacturing capacity—the chapter and verse. Nat. Biotechnol. 24:503505.
87. Kanarek, A. D. 2005. Method validation guidelines. In Guide to Bioanalytical Advances. BioPharm Int. 18:S28S33.
88. Kania, K. 2002. Blow-fill-seal packaging: a sterile environment. Pharm. Med. Packaging News September.
89. Kelley, B. 2007. Very large scale monoclonal antibody purification: the case for conventional unit operations. Biotechnol. Prog. 23:9951008.
90. Kendrick, B. S.,, J. F. Carpenter,, J. L. Cleland, and, T. W. Randolph. 1998. A transient expansion of the native state precedes aggregation of recombinant human interferon-gamma. Proc. Natl. Acad. Sci. USA 95:1414214146.
91. Kilgore, B. R.,, A. D. Lucka,, R. Patel,, B. A. Andrien, Jr., and, S. T. Dhume. 2008. Comparability and monitoring immunogenic N-linked oligosaccharides from recombinant monoclonal antibodies from two different cell lines using HPLC with fluorescence detection and mass spectrometry. Methods Mol. Biol. 446:333346.
92. Knudsen, H. L.,, R. L. Fahrner,, Y. Xu,, L. A. Norling, and, G. S. Blank. 2001. Membrane ion-exchange chromatography for process-scale antibody purification. J. Chromatogr. A 907:145154.
93. Krause, S. O. 2004. Development and validation of analytical methods for biopharmaceuticals, part I: development and optimization. BioPharm Int. 17:5261.
94. Krause, S. O. 2007. Validation of Analytical Methods for Biopharmaceuticals—a Guide to Risk Based Validation and Implementation Strategies. PDA/DHI Publishing, Bethesda, MD.
95. Krause, S. O. 2008. Formal method validation. In Guide to Analytical Methods. BioPharm Int. 21:S14S22.
96. Lam, X. M.,, J. Y. Yang, and, J. L. Cleland. 1997. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J. Pharm. Sci. 86:12501255.
97. Langer, E. S. 2008. Quantifying trends toward alternative to Protein A. BioProcess Int. 6:72.
98. Langer, E. S., and , J. Ranck. 2005. The ROI case—economic justification for disposables in biopharmaceutical manufacturing. BioProcess Int. 3:S46S50.
99. Langer, E. S., and , J. Ranck. 2006. Capacity bottleneck squeezed by downstream processes. BioProcess Int. 4:1418.
100. Li, F.,, J. Z. Zhou,, X. Yang,, T. Tressel, and, B. Lee. 2006. Current therapeutic antibody production and process optimization. BioProcess. J. 4:1625.
101. Lifely, M. R.,, C. Hale,, S. Boyce,, M. J. Keen, and, J. Phillips. 1995. Glycosylation and biological activity of CAM-PATH-1H expressed in different cell lines and grown under different culture conditions. Glycobiology 5:813822.
102. Lim, J. A. C.,, A. Sinclair,, M. Hirai, and, U. Gottschalk. 2007. Disposable membrane chromatography—counting the cost. BioPharm Int. 20:S34S40.
103. Lim, J. A. C.,, A. Sinclair,, D. S. Kim, and, U. Gottschalk. 2007. Economic benefits of single-use membrane chromatography for process-scale antibody purification. J. Chromatogr. A 907:145154.
104. Liu, X.,, M. Collins,, N. Fraud,, J. Campbell,, I. Lowenstein,, K. M. Lacki, and, A. S. Rathore. 2009. Upcoming technologies to facilitate more efficient biologics manufacturing. BioPharm Int. 22:3851.
105. Low, D.,, R. O’Leary, and, N. S. Pujar. 2007. Future of antibody purification. J. Chromatogr. B 848:4863.
106. Lubiniecki, A. S., and , P. J. Shadle. 1997. Raw material considerations. Dev. Biol. Stand. 91:6572.
107. Lucka, A. W.,, B. R. Kilgore,, R. Patel,, B. A. Andrien, Jr., and, S. T. Dhume. 2008. Mass spectrometry and HPLC with fluorescent detection-based orthogonal approaches to characterize N-linked oligosaccharides of recombinant monoclonal antibodies. Methods Mol. Biol. 446:347361.
108. Lucy, P. K., and , R. G. Beri. 2003. Key considerations in process transfer. BioProcess Int. 1:3643.
109. Luo, R.,, R. Waghmare,, M. Krishnan,, C. Adams,, E. Poon, and, D. Kahm. 2006. High-concentration UF/DF of a monoclonal antibody—strategy for optimization and scale-up. BioProcess Int. 4:4448.
110. Magari, R. T. 2002. Estimating degradation in real time and accelerated stability tests with random lot-to-lot variation: a simulation study. J. Pharm. Sci. 91:893899.
111. Magari, R. T. 2003. Assessing shelf life using real-time and accelerated stability tests. BioPharm Int. 16:3648.
112. Magari, R. T.,, K. P. Murphy, and, T. Fernandez. 2002. Accelerated stability model for predicting shelf-life. J. Clin. Lab. Anal. 16:221226.
113. Magil, S. G. 2005. Biopharmaceutical characterization techniques for early phase development of proteins. In Guide to Bioanalytical Advances. BioPharm Int. 18:S34S42.
114. Manzi, A. E. 2008. Carbohydrates and their analysis, part two: glycoprotein characterization. BioProcess Int. 6:5067.
115. Meyeroltmanns, F.,, J. Schmitz, and, M. N. Kamal. 2005. Disposable bioprocess components and single-use concepts for optimized process economy in biopharmaceutical production. BioProcess Int. 3:S60S66.
116. Mitchell, P. 2005. Next-generation monoclonals less profitable than trailblazers? Nat. Biotechnol. 23:906.
117. Moritz, A. 2005. The new GMP environment for investigational medicinal products in the European Union. BioProcess Int. 3:2838.
118. Morrow, K. J., Jr. 2001. Method for maximizing antibody yields—new technologies could help usher in lower costs and increased availability. Genet. Eng. Biotechnol. News 28 (12).
119. Nguyen, L. T.,, J. M. Wiencek, and, L. E. Kirsch. 2003. Characterization methods for the physical stability of biopharmaceuticals. PDA J. Pharm. Sci. Technol. 57:429445.
120. Niazi, S. K., and , T. L. Flynn III. 2001. A practical model for outsourced biomanufacturing. BioProcess Int. 4:S10S16.
121. Norris, D. 2008. Method for evaluating bio-container transportation applications. BioProcess Int. 6:142143.
122. Percivia. 2008. Press release: DSM and Crucell announce record achievement in PER.C6 technology. June 16. Percivia, Cambridge, MA. (Online.) http://investors.crucell.com/C/132631/PR/200806/1227870_5_5.html.
123. Polin, J. B. 2000. Doing aseptic filling in barrier isolators. Pharm. Med. Packaging News November.
124. Raju, T. S. 2003. Glycosylation variations with expression systems and their impact on biological activity of therapeutic immunoglobulins. Bioprocess Int. 1:4453.
125. Ramelmeier, R. A.,, B. D. Kelley, and , C. Van Horn. 2001. Historical, current, and future trends for validating biological processes, p. 1–11. In B. D. Kelley and, R. A. Ramelmeier (ed.), Validation of Biopharmaceutical Manufacturing Processes. American Chemical Society, Washington, DC.
126. Ransohoff, T. C. 2007. Successful strategies for production optimization. BioPharm. Int. 20:165174.
127. Rao, G.,, Y. Kostov,, A. Moreira,, D. Frey,, M. Hanson,, M. Jornitz,, O.-W. Reif,, R. Baumfalk, and , J. Qualitz. 2009. Non-invasive sensors as enablers of “smart” disposables. BioProcess Int. 7:S24S27.
128. Rathores, A. S.,, A. Wang,, M. Menon,, J. Martin,, J. Campbell, and, E. Goodrich. 2004. Optimization, scale-up, and validation issues in filtration of biopharmaceuticals. BioPharm Int. 17:4250.
129. Ray, S., and , K. Tarrach. 2008. Virus clearance strategy using a three-tier orthogonal technology platform. BioPharm Int. 21:5059.
130. Reisman, H. B. 1999. Economics, p. 273–288. In A. L. Demain and, J. E. Davies (ed.), Manual of Industrial Microbiology and Biotechnology, 2nd ed. ASM Press, Washington, DC.
131. Reynolds, G. 2006. The market need for reconstitution systems. BioProcess Int. 4:1821.
132. Robinson, C. J.,, L. E. Little, and , H.-J. Wallny. 2001. Bioassay survey 2006–2007. BioProcess Int. 6:3849.
133. Roush, D. J., and , Y. Lu. 2001. Advances in primary recovery: centrifugation and membrane technology. Biotechnol. Prog. 24:488495.
134. Russell, E.,, A. Wang, and, A. S. Rathore. 2007. Harvest of a therapeutic protein product, p. 1–58. In A. A. Shukla,, M. R. Etzel, and , S. Gadam (ed.), Process Scale Bioseparations for the Biopharmaceutical Industry. CRC Press, Boca Raton, FL.
135. Russotti, G., and , K. Goklen. 2001. Cross-flow membrane filtration of fermentation broth, p. 85–159. In W. K. Wang (ed.), Membrane Separations in Biotechnology, 2nd ed. Marcel Dekker, New York, NY.
136. Schenerman, M. A.,, J. Casas-Finet,, M. J. Axley, and, C. N. Oliver. 2003. Characterization of alternatives to animal-derived raw materials. BioProcess Int. 1:4249.
137. Schenerman, M. A.,, B. R. Sunday,, S. Kozlowski,, K. Webber,, H. Gazzano-Santoro, and, A. Miresluis. 2004. CMC startegy forum report—analysis and structure characterization of monoclonal antibodies. BioProcess Int. 2:4252.
138. Schimdt, M. T.,, S. Sze-Khoo,, A. R. Cothran,, B. Q. Thai,, S. Sargis,, B. Lebreton,, B. Kelley, and, G. S. Blank. 2009. Purification strategies to process 5 g/L titers on monoclonal antibodies. BioPharm Int. 22:S8S15.
139. Schmidt, S.,, J. Mora,, S. Dolan, and, J. Kauling. 2005. An integrated concept for robust and efficient virus clearance and contaminant removal in biotech process. BioProcess Int. 3:S26S31.
140. Schreyer, H. B.,, S. E. Miller, and, S. Rodgers. 2007. Application note: high-throughput process development. Genet. Eng. Biotechnol. News 27 (17).
141. Schwartz, L. 2003. Diafiltration for desalting or buffer exchange. BioProcess Int. 1:4349.
142. Scott, C. 2005. Methodologies for viral safety. BioProcess Int. 3:S8S14.
143. Scott, C. 2006. Process development: turning science into technology. BioProcess Int. 4:S24S41.
144. Scott, C. 2006. Formulation development: making the medicine. BioProcess Int. 4:S42S56.
145. Scott, C. 2008. In the drug delivery zone: patients are the priority. In Bio International Convention Preshow Planner. BioProcess Int. 6:S34S41.
146. Scott, C.,, S. A. Montgomery, and, L. J. Rosin. 2007. Advances in separation methods for increasing process streams. In Bio International Convention Preshow Planner. BioPharm Int. 5:S43S58.
147. Sellers, S. P., and, Y.-f. Maa. 2001. Principles of bio-pharmaceutical protein formulation. Methods Mol. Biol. 38:243263.
148. Senger, R. S., and , M. N. Karim. 2003. Effect of shear stress on intrinsic CHO culture state and glycosylation of recombinant tissue-type plasminogen activator protein. Biotechnol. Prog. 19:11991209.
149. Seymour, P. M.,, H. L. Levine, and, S. D. Jones. 2006. CMC strategies for outsourcing biopharmaceutical product manufacturing. BioProcess Int. 4:S26S29.
150. Shadle, P. J. 2004. The art of raw materials and supplier qualification. BioProcess. J. 3:4348.
151. Shadle, P. J. 2004. Qualification of raw materials for biopharmaceutical use. BioPharm Int. 17:2835.
152. Sheeley, D. M.,, B. M. Merrill, and, L. C. E. Taylor. 1997. Characterization of monoclonal antibody glycosylation: comparison of expression systems and identification of terminal a-linked galactose. Anal. Biochem. 247:102110.
153. Shi, L.,, Q. Chen,, L. A. Norling,, A. S. Lau,, S. Krejci, and, Y. Xu, 2004. Real-time quantitative PCR as a method to evaluate xenotropic murine leukemia virus removal during pharmaceutical protein purification. Biotechnol. Bioeng. 87:884896.
154. Shipston, N. 2006. Technical transfer of manufacturing processes from client sites to a CMO. BioProcess Int. 4:S40S42.
155. Shukla, A. A.,, B. Hubbard,, T. Tressel,, S. Guhan, and, D. Low. 2007. Downstream processing of monoclonal antibodies—application of platform technologies. J.Chromatgr. B 848:2839.
156. Shukla, A. A., and , J. R. Kandula. 2008. Harvest and recovery of monoclonal antibodies from large-scale mammalian cell culture. BioPharm Int. 21:3446.
157. Simmerman, H., and , R. Donnelly. 2005. Defining your product profile and maintaining control over it, part 1. BioProcess Int. 3:3238.
158. Smith, K. A. 2006. Considerations for aseptic filling of parenterals. BioProcess Int. 4:1217.
159. Sofer, G. 2004. Validation issues for disposable manufacturing. BioProcess Int. 2:S18S20.
160. Sofer, G.,, D. C. Lister, and, J. A. Boose. 2003. Inactivation methods grouped by virus: virus inactivation in the 1990s—and into the 21st century. BioPharm Int. 16:S37S42.
161. Some, I.,, P. Bogaerts,, R. Hanus,, M. Hanocq, and, J. Dubois. 2001. Stability parameter estimation at ambient temperature from studies at elevated temperatures. J. Pharm. Sci. 90:17591766.
162. Steffy, C. P. 2003. What are the options? BioProcess Int. 1:2S11S.
163. Strancar, A.,, A. Podgornik,, M. Barut, and, R. Necina. 2002. Short monolithic columns as stationary phases for bio-chromatography. Adv. Biochem. Eng. Biotechnol. 76:4985.
164. Tarrach, K.,, A. Meyer,, J. E. Dathe, and, H. Sun. 2007. The effect of flux decay on a 20-nm nanofilter for virus retention. BioPharm Int. 20:S15S18.
165. Tipton, B.,, J. A. Boose,, W. Larsen,, J. Beck, and , T. O’Brien. 2001. Retrovirus and parvovirus clearance from an affinity column product using adsorptive depth filtration. BioPharm Int. 15:4350.
166. United states Pharmacopeia. 2001. Analytical instrument qualification (draft). Pharmacopeial Forum 31:15.
167. Valax, P.,, E. Charbaut,, J. E. Dathe,, K. Tarrach,, A. Lamproye, and, H. Broly. 2009. Robustness of parvovirus-retentive membranes and implications for virus clearance validation requirements. BioProcess Int. 7:S56S62.
168. Van Reis, R., and, A. Zydney. 2001. Membrane separations in biotechnology. Curr. Opin. Biotechnol. 12:208211.
169. Vogt, R., and , T. Paust. 2009. Disposable factory or tailor made integration of single-use systems? BioProcess Int. 7:S72S77.
170. Wallace, K. K., and , A. R. Moreira. 1998. Changes in biologics regulation: impact on the development and validation of the manufacturing processes for well-characterized products, p. 170–179. In B. D. Kelley and, R. A. Ramelmeier (ed.), Validation of Biopharmaceutical Manufacturing Processes. American Chemical Society, Washington, DC.
171. Wang, A.,, R. Lewus, and, A. Rathore. 2006. Comparison of different options for harvest of a therapeutic protein product from high cell density yeast fermentation broth. Biotechnol. Bioeng. 94:91104.
172. Wang, J.,, T. Diehl,, M. Watkins-Fischl,, D. Perkins,, D. Aguiar, and, A. Arunakumari. 2008. Optimizing the primary recovery step in nonaffinity purification schemes of HuMAbs. Suppl. BioPharm Int. 21:S4S10.
173. Wang, N.,, B. Hu,, R. Ionescu,, H. Mach,, J. Sweeney,, C. Hamm,, M. J. Kirchmeier, and, B. K. Meyer. 2009. Opalescence of an IgG1 monoclonal antibody formulation is mediated by ionic strength and excipients. BioPharm Int. 22:3647.
174. Webb, S. D.,, J. N. Webb,, T. G. Hughes,, D. F. Sesin, and, A. C. Kincaid. 2002. Freezing bulk-scale biopharmaceuticals using common techniques—and the magnitude of freeze-concentration. BioPharm Int. 15:2234.
175. Weinberg, S., and , S. J. Advant. 2009. Serving two masters: reconciling EMEA/GAMP 5 and FDA/cGMP Phase 1. BioPharm Int. 22:2425.
176. Whitford, W. G. 2005. Lipids in bioprocess fluids. BioProcess Int. 3:4656.
177. Wilson, J. S. 2006. A fully disposable monoclonal antibody manufacturing train. BioProcess Int. 4:S34S36.
178. Winter, W. 2006. Analytical instrument qualification: standardization on the 4Q model. BioProcess Int. 4:4650.
179. Wolk, B.,, P. Bezy,, R. Arnold, and, G. Blank. 2003. Characteristics of a good antibody manufacturing process. BioProcess Int. 1:5058.
180. Yavorsky, D.,, R. Blanck,, C. Lambalot, and, R. Brunkow. 2003. The clarification of bioreactor cell cultures for bio-pharmaceuticals. Pharm. Technol. 27:6274.
181. Yigzaw, Y.,, M. Tranh,, R. Riper, and, A. Shukla. 2006. Exploitation of the adsorptive properties of depth filters for host cell protein removal during monoclonal antibody purification. Biotechnol. Prog. 22:288296.
182. Yuan, Q. S.,, A. Rosenfeld,, T. W. Root,, D. J. Klingenberg, and, E. N. Lightfoot. 1999. Flow distribution in chromato-graphic columns. J. Chromatogr. A 831:149165.
183. Zhang, W., and , M. J. Czupryn. 2002. Free sulfhydryl in recombinant monoclonal antibodies. Biotechnol. Prog. 18:509513.
184. Zhang, L.,, M. Moo-Young, and, C. P. Chou. 2008. Stability improvement of a therapeutic protein by reducing agent treatment. Chinese J. Biotechnol. 24:21422143.
185. Zhou, J. X.,, S. Dermawan,, F. Solamo,, G. Flynn,, R. Stenson,, T. Tressel, and, S. Guhan. 2007. pH-conductivity hybrid gradient cation-exchange chromatography for process-scale monoclonal antibody purification. J. Chromatogr. A 1175:6980.
186. Zhou, J. X., and , T. Tressel. 2005. Membrane chromatography as a robust purification system for large-scale antibody production. BioProcess Int. 3:S32S37.
187. Zhou, J. X., and , T. Tressel. 2006. Basic concepts in Q membrane chromatography for large-scale antibody production. Biotechnol. Prog. 22:341349.
188. Zhou, J. X.,, T. Tressel,, U. Gottschalk,, F. Soalmo,, A. Pastor, and, S. Dermawan. 2006. New Q membrane scale-down model for process-scale antibody purification. J. Chromatogr. A 1134:6673.
189. Zhou, J. X.,, T. Tressel, and, S. Guhan. 2007. Disposable chromatography. BioPharm Int. 20:S25S33.

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