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Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

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Lyophilized Biologics and Vaccines

Abstract

The quality-by-design (QbD) approach enables the robust development of the lyophilization cycle in an effective manner where deep understanding is gained through building a scalable freezing step in terms of ice nucleation along with the generation of a primary drying design space. Applying QbD to the design of the cycle allows for the consideration of scalability up front, removing the traditional “trial-and-error” approach, while understanding the performance of the large-scale freeze-dryer. To achieve this, the heat transfer coefficient (K v) of the vial and the product cake resistance (R p) are needed for the mathematical modeling in order to obtain an accurate design space. This chapter explores the latest development and scale-up of the lyophilization process for protein therapeutics in the vial using a QbD approach. Ice nucleation, heat and mass transfer, lyophilization cycle design, and scalability are discussed. A case study is presented for a protein product using both theoretical modeling and experimental scale-down model approach to obtain a wide design space.

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Acknowledgments

The authors would like to acknowledge Arun Jangda (Genzyme, Framingham) for the small-scale lyophilization data and George Gregory (Genzyme, Waterford) for the heat transfer data. The authors would also like to thank Mark Yang, PhD and the Genzyme Late Stage Process Development group located at Framingham, MA; Martin Addo, PhD and the Genzyme Technical Development (MS&T) group located at Waterford, Ireland. The authors would like to thank Jean-Rene Authelin of Sanofi R&D for his input.

Author information

Authors and Affiliations

  1. Late Stage Process Development, Genzyme, A Sanofi Company, 01701, Framingham, MA, USA

    Bingquan (Stuart) Wang

  2. Protein Formulation Development, Biogen Idec, 15 Cambridge Center, 02142, Cambridge, MA, USA

    Bingquan (Stuart) Wang

  3. Technical Development, Genzyme Ireland Ltd, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

    Timothy R. McCoy

  4. Department of Pharmaceutical Sciences, University of Connecticut, 06269, Storrs, CT, USA

    Michael J. Pikal

  5. Novartis Vaccines and Diagnostics, 475 Green Oaks Parkway, 27540, Holly Springs, NC, USA

    Dushyant Varshney

  6. MS & T Hospira, Inc., 275 N. Field Drive Lake Forest, 60045, Lake Forest, IL, USA

    Dushyant Varshney

Authors
  1. Bingquan (Stuart) Wang
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  2. Timothy R. McCoy
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  3. Michael J. Pikal
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  4. Dushyant Varshney
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Corresponding author

Correspondence to Bingquan (Stuart) Wang .

Editor information

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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Wang, B., McCoy, T., Pikal, M., Varshney, D. (2015). Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design. In: Varshney, D., Singh, M. (eds) Lyophilized Biologics and Vaccines. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2383-0_7

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