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Advances in Process Analytical Technology in Freeze-Drying

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Lyophilized Biologics and Vaccines

Abstract

Process analytical technology (PAT) is an integral part of quality by design (QbD), and it allows the online monitoring of critical process parameters to ensure acceptable product quality attributes. This chapter provides a systematic review of latest PAT tools for freeze-drying, with emphasis on suitability for large-scale manufacturing process. Common process monitoring devices such as product temperature sensors (including wireless sensors), Pirani gauge, manometric temperature measurement (MTM), tunable diode laser adsorption spectroscopy (TDLAS), plasma emission spectroscopy (Lyotrack), near-infrared (NIR), and Raman et al. are reviewed in terms of the operation mechanism, major applications, and limitations. These PAT tools are then compared based on their capabilities, practical advantages, and scalability to a large-scale freeze dryer. The criteria of an “ideal” future PAT tool for freeze-drying are then proposed in order to be compliant with the QbD requirements. Finally, the current status of PAT implementation in both development scale and manufacturing scale lyophilizer is discussed, and future implementation of promising PAT tools is proposed.

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Author information

Authors and Affiliations

  1. Late Stage Process Development, Genzyme, A Sanofi Company, 45 New York Ave, 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

Authors
  1. Bingquan (Stuart) Wang
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  2. Timothy R. McCoy
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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. (2015). Advances in Process Analytical Technology in Freeze-Drying. In: Varshney, D., Singh, M. (eds) Lyophilized Biologics and Vaccines. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2383-0_8

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