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Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer

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Abstract

Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient, Kv, and the cake resistance, Rp. The classical gravimetric method used to measure Kv is tedious, time- and resource-consuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both Kv and Rp directly from an experimental run (e.g., temperature and Pirani profiles). The new methodology is demonstrated using 5% w/v mannitol model system. The values of Kv obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing.

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Funding

This study was funded by AbbVie Inc. AbbVie is responsible for the study design, research, data collection, analyses, and interpretation of data, as well as writing, reviewing, and approving the publication.

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Authors and Affiliations

  1. Development Sciences, Research and Development, AbbVie Inc., 1 N Waukegan Road, North Chicago, Illinois, 60064, USA

    Deliang Zhou, Feroz Jameel, Kushal Sinha & Nandkishor K. Nere

  2. Science and Technology, Operations, AbbVie Inc., 1 N Waukegan Road, North Chicago, Illinois, 60064, USA

    Sherwin Shang & Ted Tharp

Authors
  1. Deliang Zhou
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  2. Sherwin Shang
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  3. Ted Tharp
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  4. Feroz Jameel
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Correspondence to Deliang Zhou.

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All authors are AbbVie employees and may own AbbVie stock.

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Zhou, D., Shang, S., Tharp, T. et al. Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer. AAPS PharmSciTech 20, 263 (2019). https://doi.org/10.1208/s12249-019-1478-9

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  • DOI: https://doi.org/10.1208/s12249-019-1478-9

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