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

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Quality by Design for Biopharmaceutical Drug Product Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 18))

Abstract

This chapter provides a description of the motivation for the development and application of real-time, on-line 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 25.1. 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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Acknowledgements

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.

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Authors and Affiliations

  1. Parenteral Product and Process Development, Amgen Inc., Mail stop 30W-2-A, One Amgen Center Drive, 91320, 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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Corresponding author

Correspondence to Feroz Jameel .

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Editors and Affiliations

  1. Parenteral Product and Process Development, Amgen Inc., Thousand Oaks, California, USA

    Feroz Jameel

  2. Bill and Melinda Gates Foundation, Chemistry, Manufacturing and Controls, Seattle, Washington, USA

    Susan Hershenson

  3. Division of Product Quality Research, Food and Drug Administration, Center for Drug Evaluation and Research, Office of Testing and Research and Office of Pharmaceutical Sciences, Silver Spring, Maryland, USA

    Mansoor A. Khan

  4. Enterprise Catalyst Group Inc., Palo Alto, California, USA

    Sheryl Martin-Moe

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Jameel, F., Kessler, W., Schneid, S. (2015). Application of PAT in Real-time Monitoring and Controlling of Lyophilization Process. In: Jameel, F., Hershenson, S., Khan, M., Martin-Moe, S. (eds) Quality by Design for Biopharmaceutical Drug Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 18. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2316-8_25

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