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Quality by Design for Biopharmaceutical Drug Product Development pp 565–593Cite as

Using Mathematical Modeling and Prior Knowledge for QbD in Freeze-Drying Processes

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

Abstract

This chapter deals with the use of mathematical modeling to get quality-by-design in a freeze-drying process. The target is to identify the design space of the process, i.e., the values of the operating conditions that allow maintaining product temperature below the limit value during primary and secondary drying stages, with a sublimation rate compatible with the capacity of the condenser, avoiding choking flow in the duct connecting the chamber to the condenser, minimizing drying duration, and getting the target value of residual moisture in the final product. Mathematical models of product evolution in the vials during the whole process, and of the freeze-drying equipment, are presented, and the experimental investigation required to get the values of model parameters is discussed, pointing out that model accuracy and level of parameters uncertainty influence the quality of the results. Then, the use of mathematical models to calculate the design space for primary and secondary drying stages is presented, pointing out how the design space can be used to optimize the cycle and to analyze the effect of any deviation of process variables from their set-point values.

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Acknowledgements

The contribution of Daniele Marchisio (Politecnico di Torino) and the support of Telstar Technologies S.L. (Spain) for the CFD study of the freeze-dryer is gratefully acknowledged.

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Authors and Affiliations

  1. Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, 10129, Torino, corso Duca degli Abruzzi 24, Italy

    Davide Fissore, Roberto Pisano & Antonello A. Barresi

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  1. Davide Fissore
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  2. Roberto Pisano
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  3. Antonello A. Barresi
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Corresponding author

Correspondence to Davide Fissore .

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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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Fissore, D., Pisano, R., Barresi, A. (2015). Using Mathematical Modeling and Prior Knowledge for QbD in Freeze-Drying Processes. 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_23

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