(418o) CFD Modeling of Commercial Scale Thawing Time from Small Scale Bags

It is imperative that the parameters required for  the thawing of the frozen formulated drug substance (FFDS)  be thoroughly evaluated and optimized before transferring the process to commercial DP manufacturing site. This unit operation contributes the most to the process parameter, time out of refrigeration (TOR), which is typically a CPP for biopharmaceuticals due to instability upon exposure to ambient temperature. The thawing time of a monoclonal antibody has been studied in a 30mL bag to obtain difficult to measure parameters (by incorporating into the model) like heat transfer coefficient, heat capacity, conductivity and thawing heat which are same for any scale provided the material of construction, composition of substance being thawed and the thawing procedure are consistent.  These parameters are then incorporated into the thawing model for a commercial scale configuration (6 L bag) to predict the thawing time and temperature-time profile during thawing. This model can also capture the change in liquid volume fraction with time and has the potential to accommodate both dynamic and static thawing.