Chapter 19: Design of a Bulk Freeze-Thaw Process for Biologics
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Because of their marginal stability in the liquid state, biologic solutions are stored and shipped frozen to enhance stability and operational flexibility for further processing. During the freezing process, protein solutions can undergo denaturation through various pathways depending upon the scale and technologies used. In this chapter, the physics of freezing, various modes of denaturation, and technologies available for large-scale freeze-thaw process are discussed. Practical solutions to address and mitigate the problems are also recommended with illustrations.
KeywordsFreezing Thawing Cryoconcentration Cold denaturation Proteins Controlled rate freeze-thaw Uncontrolled rate freeze-thaw Carboys Celsius bags CryoVessel
- 1.Schmidt DJ, Akers MJ. Cryogranulation: a potential new final process for bulk drug substances. Biopharm. 1997;10:28–32.Google Scholar
- 11.Franks F, Auffret T. Freeze-drying of pharmaceuticals and biopharmaceuticals: principles and practice. London: The Royal Society of Chemistry; 2008.Google Scholar
- 13.Kapil Gupta NR, Barron L, Ji W, Jameel F, Murphy K. Assessment of protein stability during freeze-thaw process. In: ACS Fall National Meeting. Boston; 2007.Google Scholar
- 15.Bradley R. Plotting freezing curves for frozen desserts. Dairy Rec. 1984;85:114–5.Google Scholar
- 17.Jameel F, Searles J. Development and optimization of the freeze-drying processes. In Formulation and process development strategies for manufacturing biopharmaceuticals; 2010. John Wiley & Sons, Ltd: Hoboken, New Jersey.Google Scholar
- 18.Pikal MJ. Freeze-drying of proteins. Part II: Formulation selection. BioPharm. 1990;3(9):26–30.Google Scholar
- 20.Becktel, WJ, Schellman JA. Protein stability curves. Biopolymers. 1987; 26:1859–1877. https://doi.org/10.1002/bip.360261104.
- 29.Carpenter JF, Izutsu K, Randolph TW. Freezing and drying-induced perturbations of protein structure and mechanisms of protein protection by stabilizing additives. In: Rey L, May JC, editors. Freeze-drying/lyophilization of pharmaceutical and biological products, vol. 96. New York: Marcel Dekker, Inc; 1999.Google Scholar
- 30.Carpenter JF, et al. Rational design of stable lyophilized protein formulations: theory and practice. In: Carpenter JF, Manning MC, editors. Rational design of stable protein formulations, Pharmaceutical biotechnology, vol. 13: Springer; 2002.Google Scholar
- 31.Wilkins J, Sesin D, Wisniewski R. Large-scale cryopreservation of biotherapeutic products. Innov Pharm Technol. 2001;1:174–80.Google Scholar
- 37.MG Scientific supplying laboratories. http://www.mgscientific.com/service/plastics.asp.
- 38.Nail SL, et al. Fundamentals of freeze-drying in development and manufacture of protein pharmaceuticals, ed. S.L. Nail and M.J. Akers. 2002:281–360.Google Scholar