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

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.