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Application of PAT in Real-Time Monitoring and Controlling of Lyophilization Process

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Principles and Practices of Lyophilization in Product Development and Manufacturing

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 59))

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Abstract

This chapter provides a description of the motivation for the development and application of real-time, online process monitoring techniques for pharmaceutical lyophilization. A high level survey of both batch average and single vial measurement techniques is provided and is summarized in Table 1. Many of these techniques have been used for decades, but a few new measurement techniques have been recently introduced, including gas plasma spectroscopy (Lyotrack) and tunable diode laser absorption spectroscopy (LyoFlux). A detailed description of the TDLAS technique is provided, including a description of the spectroscopy principles that underpin the development and application of the measurement technique. TDLAS measurements have been combined with established heat and mass transfer models to provide determinations of important in-process product parameters such as product temperature and product resistance to drying. Additional experimentation is required to demonstrate the application of this and other new techniques within manufacturing scale dryers, allowing the use of PAT tools from laboratory scale process development through scale-up to routine monitoring and control of product manufacturing. Continued application of PAT tools will result in improved product quality and should ultimately lead to improved efficiency and lower production costs.

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Acknowledgments

Partial financial support for the development and application of the TDLAS mass flow rate sensor to monitoring pharmaceutical lyophilization was provided by the National Science Foundation (NSF) and The National Institutes of Health, National Cancer Institute (NIH/NCI) Small Business Innovative Research (SBIR) programs.

The TDLAS sensor development and applications described within this chapter resulted from the dedicated work of numerous individuals at Physical Sciences Inc.: W.J Kessler, G.E. Caledonia, M.L. Finson, J.F. Cronin, P.A. Mulhall, S.J. Davis, D. Paulsen, J.C. Magill, K.L. Galbally-Kinney, J.A. Polex, T. Ustun, A.H. Patel, D. Vu, A. Hicks, and M. Clark; The University of Connecticut: M.J. Pikal, H. Gieseler, S. Schneid, S.M. Patel, S. Luthra; and IMA Edwards: A. Schaepman, D.J. Debo, V. Bons and F. Jansen.

Author information

Authors and Affiliations

  1. Amgen Inc, 1 Amgen Center Dr., Thousand Oaks, CA, USA

    Feroz Jameel

  2. Physical Sciences Inc, Andover, MA, USA

    William J. Kessler

  3. Syntacoll GmbH, Saal, Germany

    Stefan Schneid

Authors
  1. Feroz Jameel
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  2. William J. Kessler
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  3. Stefan Schneid
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Editors and Affiliations

  1. Nimble BioSolutions, Gurnee, IL, USA

    Feroz Jameel

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Jameel, F., Kessler, W.J., Schneid, S. (2023). Application of PAT in Real-Time Monitoring and Controlling of Lyophilization Process. In: Jameel, F. (eds) Principles and Practices of Lyophilization in Product Development and Manufacturing . AAPS Advances in the Pharmaceutical Sciences Series, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-031-12634-5_19

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