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Process Scale-Up and Optimization of Lyophilized Vaccine Products

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Lyophilized Biologics and Vaccines

Abstract

Vaccine, in general, is our best defense against infectious diseases and represents one of the greatest success stories responsible for the reduction of infectious diseases. Relative to therapeutic proteins (TPs) and small molecules, vaccine drug product development is more challenging and it is often stated that the “process is product” especially for live virus vaccines (LVVs). Given the global outreach of vaccines and the corresponding impact on human health, a well-defined systematic approach must be used to achieve a global target product profile (GTPP) that is not only safe and efficacious but also delivers on the intended market demands while keeping customer centricity in mind (e.g., thermostability, delivery devices/images, etc.). This chapter intends to share our findings for attaining GTPP for lyophilized vaccine products by sharing commonly used guidelines and approaches (e.g., quality by design (QbD), process analytical testing (PAT), design of experiment (DOE), etc.) for end-to-end development of lyophilized vaccine products (from preformulation to commercialization). Specifically, technical aspects of a laboratory scale lyophilization process and scale-up challenges are described as they pertain to various manufacturing unit operation and good manufacturing practice (GMP), quality, and operations systems within each manufacturing environment. In addition, suitable case studies demonstrating the impact of (a) a lyophilization loading process for a commercial cabinet and (b) equipment/facility considerations during a transfer/scale-up process on products’ critical quality attributes (CQAs) are discussed.

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Author information

Authors and Affiliations

  1. Telford, USA

    Jeffrey T. Blue

  2. Collegeville, USA

    Jessica R. Sinacola

  3. Greater Philadelphia Area, USA

    Akhilesh Bhambhani

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  1. Jeffrey T. Blue
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  2. Jessica R. Sinacola
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  3. Akhilesh Bhambhani
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Correspondence to Jeffrey T. Blue .

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Editors and Affiliations

  1. Novartis Vaccines and Diagnostics, Holly Springs, North Carolina, USA

    Dushyant Varshney

  2. Novartis Vaccines and Diagnostics, Holly Springs, North Carolina, USA

    Manmohan Singh

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Blue, J., Sinacola, J., Bhambhani, A. (2015). Process Scale-Up and Optimization of Lyophilized Vaccine Products. In: Varshney, D., Singh, M. (eds) Lyophilized Biologics and Vaccines. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2383-0_9

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