Abstract
Preservation through freezing is routinely used in the food industry. The same strategy can also be applied to biotechnology protein based drugs. However, in this case, careful considerations must be given to the process as the freeze and thaw operations put additional stresses on the protein, which may have negative impact on its function. In this chapter, we present a Quality by Design (QbD) approach for handling the risks associated with a commercial production freeze-thaw process for recombinant protein drug substances. A brief treatment on the physics of freezing and thawing is given, followed by a description of the commercial freeze-thaw unit operation and associated equipment. The QbD risk-based strategy is then discussed in detail. The overall approach is illustrated through a case study that shows how small-scale models are leveraged for characterization of freeze-thaw production process.
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Lam, P., Lim, F., Sane, S. (2015). Drug Substance Frozen Storage and Thawing. In: Jameel, F., Hershenson, S., Khan, M., Martin-Moe, S. (eds) Quality by Design for Biopharmaceutical Drug Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 18. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2316-8_9
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DOI: https://doi.org/10.1007/978-1-4939-2316-8_9
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