Downstream Precipitate Characterization in Continuous Bioprocessing

David Sherr of AstraZeneca presents, Downstream Precipitate Characterization in Continuous Bioprocessing, describing how neutralization of a bispecific antibody product led to significant precipitate formation, with particle size and distribution affecting depth filter capacity and fouling mechanisms. The study emphasized the need to understand and control these parameters for successful scale-up.

EasyViewer and iC Vision software were used to monitor real-time changes in particle chord length distribution at different pH values, revealing that higher pH led to larger particles and improved filter capacity, while lower pH produced finer particles that clogged filters more rapidly. The team developed a deep learning model for microscopy images to segment and quantify particle size, surface area, and sphericity over time, confirming that particles grew larger and less spherical with extended mixing, consistent with EasyViewer observations.

Both EasyViewer and in-house microscopy provided complementary data, with EasyViewer offering inline, real-time monitoring suitable for process control, and microscopy enabling detailed characterization with smaller sample volumes. The combined approach increased confidence in process understanding and tech transfer. The findings informed operational decisions, such as mixing duration before filtration, and provided a framework for responding to regulatory and operational queries regarding precipitate behavior and filter performance in continuous bioprocessing.