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Chapter 7: An Empirical Phase Diagram: High-Throughput Screening Approach to the Characterization and Formulation of Biopharmaceuticals

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Development of Biopharmaceutical Drug-Device Products

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 35))

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Abstract

The complexity of proteins usually requires the use of multiple, moderate resolution experimental techniques to provide an information-rich picture of their structure and stability. Here we describe a technique known as the empirical phase diagram (EPD), which can be used to present such multidimensional data in picture form. Data from various spectroscopic, hydrodynamic, and calorimetric methods, among others, are created in matrix form and converted to a colored picture as a function of variables such as temperature, pH, ionic strength, etc. Additional methods such as radar charts and Chernoff faces are also discussed. The use of EPDs in the characterization and formulation of biomolecules is described. Further methods based on machine learning are also considered. A wide range of examples are employed to illustrate the power and utility of these approaches.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS, USA

    Yangjie Wei, Sangeeta B. Joshi, Akhilesh Bhambhani, Yuhong Zeng, Nicholas R. Larson, Gang Hu & C. Russell Middaugh

  2. Merck & Co. Inc., West Point, PA, USA

    Akhilesh Bhambhani

  3. ReForm Biologics, Woburn, MA, USA

    Yuhong Zeng

  4. Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA

    Eric J. Deeds

  5. Center for Computational Biology, University of Kansas, Lawrence, KS, USA

    Eric J. Deeds

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  1. Yangjie Wei
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  2. Sangeeta B. Joshi
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  3. Akhilesh Bhambhani
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  4. Yuhong Zeng
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  5. Nicholas R. Larson
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  6. Gang Hu
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  7. Eric J. Deeds
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  8. C. Russell Middaugh
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Corresponding author

Correspondence to C. Russell Middaugh .

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Editors and Affiliations

  1. Formulation Development New Biological Entities, AbbVie (United States), North Chicago, IL, USA

    Feroz Jameel

  2. Drug Product Development (Retired), AbbVie (United States), North Chicago, IL, USA

    John W. Skoug

  3. Combination Product Development, AbbVie, Inc., North Chicago, IL, USA

    Robert R. Nesbitt

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Wei, Y. et al. (2020). Chapter 7: An Empirical Phase Diagram: High-Throughput Screening Approach to the Characterization and Formulation of Biopharmaceuticals. In: Jameel, F., Skoug, J., Nesbitt, R. (eds) Development of Biopharmaceutical Drug-Device Products. AAPS Advances in the Pharmaceutical Sciences Series, vol 35. Springer, Cham. https://doi.org/10.1007/978-3-030-31415-6_7

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