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Chapter 17: Scale-Down Models for Robust Biologics Drug Product Process Development

  • Smeet DeshmukhEmail author
  • Maria O. Ogunyankin
Chapter
  • 67 Downloads
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 35)

Abstract

The objective of process development is to build robustness and demonstrate control of a manufacturing process to ensure consistent biological products within the specifications of its quality attributes. The new regulatory expectation and quality by design (QbD) principles laid out also reinforce the need for systematic process development approach and risk assessment to be done early and throughout the development. Biologics drug product manufacturing process and unit operations involved need to be well understood, characterized in terms of different stresses and critical process parameters that would impact their critical quality attributes. This chapter focuses on the approach of utilizing combination of small-scale/minipiloting tools and scale-down models (miniaturization of large-scale equipment) for process development of ready-to-use liquid drug product. The small-scale tools require minimal amount of materials to understand the sensitivity of molecules to the different stresses and quantify the limits of each of those stresses that the molecules can be exposed to during manufacturing. The scale-down models for each unit operation are discussed in detail with the suggestion of experimentation involving key process parameter variation to help define the process design space. Some relevant case studies are covered to explain the utility of the models and the resultant control strategy that can be put in place for robust drug product manufacturing.

Keywords

Process risk assessment Minipiloting tools Shear stress Interfacial stress Light stress Freeze–thaw Mixing Filtration and pumping 

Notes

Acknowledgments

The authors want to thank Masano Huang, Andrew Ilott, Melissa Bentley, Kristine Rafferty, Johnathan Goldman, Mary Krause, Thiago Carvalho, Brenda Remy, and Mehrnaz Khossravi for their helpful discussion and collaboration on some of the experiments captured in the chapter.

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Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  1. 1.Pharmaceutical Sciences, Merck & Co. Inc.KenilworthUSA
  2. 2.Drug Product Science & Technology, Bristol-Myers Squibb, Co.New BrunswickUSA

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