Practical Considerations for High Concentration Protein Formulations

  • Deirdre Murphy Piedmonte
  • Jian Hua Gu
  • Stephen R. Brych
  • Monica M. GossEmail author
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 38)


Practical issues that arise for high concentration protein formulations can complicate manufacturing and affect injectability/device compatibility. High concentration protein formulations have an increased tendency for high solution viscosity, physical stability sensitivities (aggregation/particulation), and non-Newtonian solution behavior (shear thinning) due to high shear rates. Process unit operations can be negatively impacted by these factors, and it is critical to understand how they influence process performance. Device compatibility can be affected by changes in protein concentration and temperature that will impact product viscosity and injectability. Complete characterization of the solution physical properties (viscosity and shear thinning profile) as well as the stability profile must be understood to ensure efficient processing, delivery, and efficacy of the therapeutic product. If potential candidates with impeding viscosity values are not identified early in development, subsequent mitigation efforts to reduce viscosity likely pivot from a protein engineering approach to changes in formulation.


High protein concentration formulation Viscosity Shear thinning Device compatibility Injectability Syringeability 



The authors wish to acknowledge the work of Drs. Nitin Rathore and Joseph Bernacki, particularly their data visualization, as Fig. 7.1 was adapted from their work. Thanks to Dr. Nicholas Clark for generating breakloose extrusion data. We would also like to thank Dr. Sugunakar Patro for his critical review and support.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Deirdre Murphy Piedmonte
    • 1
  • Jian Hua Gu
    • 1
  • Stephen R. Brych
    • 1
  • Monica M. Goss
    • 1
    Email author
  1. 1.Amgen, Inc., Process DevelopmentOne Amgen Center DriveThousand OaksUSA

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