Abstract
Lyophilization has become an important part of the biopharmaceutical industry as more biological entities are being explored as therapeutic agents. For biologics, whose formulation and storage in aqueous solution result in instability, lyophilization represents the most common and important formulation strategy to improving their long-term stability. The process of lyophilization is a complex, multistep process that requires a sound understanding of both product and process-related attributes to ensure higher operational efficiency and consistently acceptable final product.
This chapter provides an overview of the application of quality by design (QbD) principles to the lyophilization of biologics from a Food and Drug Administration (FDA) science perspective. Unlike other unit operations in several dosage form development, lyophilization is not a very-well-understood process. It is critical that the process is well understood to obtain a product that consistently meets the labeled therapeutic claim. In this chapter, there is particular focus on the key steps in the application of QbD with specific examples as applied to the lyophilization of a model monoclonal antibody, as well as the application of process analytical technology (PAT) tools for monitoring and control of the process.
Keywords
- Lyophilization
- Quality by design
- Process analytical technology
- Design space
- Biologics
- Monoclonal antibody
- Freezing
- Primary drying
- Secondary drying
- Critical quality attributes
The views expressed in this chapter are those of the authors and do not necessarily represent the position of the Agency.
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Awotwe-Otoo, D., Khan, M. (2015). Lyophilization of Biologics: An FDA Perspective. In: Varshney, D., Singh, M. (eds) Lyophilized Biologics and Vaccines. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2383-0_15
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DOI: https://doi.org/10.1007/978-1-4939-2383-0_15
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