(184e) Precipitant Surprise! Investigation and Mitigation of Media Precipitation during Scale-up and Technology Transfer

Biopharmaceutical media powders are increasing in complexity to aid in increased cell densities and provide muti-cell platform utility. When hydrated, these complex powders produce high concentration solutions that are composed of dissolved and dispersed raw materials with difficult to predict solubility limits, complex chemistries, and challenging hydration procedures. Precipitation issues can arise or be discovered during technology transfer due to variations in hydration procedure and/or increased visibility at scale. Small-scale models for media hydration, coupled with chemical characterization techniques were used to identify the root cause of media precipitation. The isolated precipitates were analyzed by FTIR and EDX methods to understand their chemical characteristics. Experiments were performed to replicate the media precipitate formation, to different levels, by varying several parameters of the media hydration process and capturing their impact on turbidity, osmolality, component concentration via Cedex BioHT, Focused Beam Reflectance Measurement (FBRM), and Charged Aerosol Detection (CAD) signals throughout the hydration process. The small-scale studies and DOEs helped identify several hydration process parameters that impacted media precipitate formation. Implementation of the appropriate set of conditions for these parameters at scale resulted in a reduction in the amount of precipitation observed.