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Advances in Instrumental Analysis Applied to the Development of Lyophilization Cycles

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Lyophilized Biologics and Vaccines

Abstract

This chapter discusses the development of pharmaceutical product lyophilization cycles based on the coupling of process and product attributes. Cycle development is framed in the context of the recent International Conference on Harmonization Q8 R2 guidance and the quality-by-design (QbD) approach which focuses on the generation of a design space using well-known heat and mass transfer principles. The chapter briefly reviews analytical approaches used to determine critical product formulation attributes, such as the collapse temperature, and provides detailed information on a new approach to determine the collapse temperature, optical coherence tomography freeze-drying microscopy (OCT-FDM). OCT-FDM enables determination of the collapse temperature in a vial rather than a thin film, providing an improved determination approach in a relevant container system. Tunable diode laser absorption spectroscopy (TDLAS) water vapor mass flow measurements for determining both equipment limitations and product temperature behavior measurements are described. These measurements can be combined with the heat and mass transfer mathematical model to enable the determination of key process attributes during drying that affect process design and product quality.

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Acknowledgments

Figure 2 of the chapter was developed by inputs from Timothy R McCoy. The OCT-FDM development and application resulted from the dedicated work of numerous individuals at Physical Sciences Inc.: Mircea Mujat, William J. Kessler, R. Daniel Ferguson, Nicusor Iftimia, Daniel X. Hammer, Kristin Galbally-Kinney, Phillip Mulhall and Ankit Patel and The University of Connecticut: Kristyn Greco, Puneet Sharma and Michael J. Pikal.

Partial financial support for the development and application of the Optical Coherence Tomography Freeze Drying Microscopy (OCT-FDM) and Tunable Diode Laser Absorption Spectroscopy systems was provided by the National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering and National Cancer Institute Small Business Innovative Research Programs (awards R44EB010317 and HHSN261200900023C). The content of this chapter is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Physical Sciences Inc., 20 New England Business Center, 01810-1077, Andover, MA, USA

    William J. Kessler & Mircea Mujat

  2. Genentech Inc., 500 Forbes Boulevard, 94080, South San Francisco, CA, USA

    Puneet Sharma

Authors
  1. William J. Kessler
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  2. Puneet Sharma
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  3. Mircea Mujat
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Correspondence to William J. Kessler .

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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Kessler, W., Sharma, P., Mujat, M. (2015). Advances in Instrumental Analysis Applied to the Development of Lyophilization Cycles. In: Varshney, D., Singh, M. (eds) Lyophilized Biologics and Vaccines. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2383-0_4

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