High-throughput systems have been used in mammalian cell line and process development optimization activities during the biopharmaceutical drug development.1 However, during process characterization, bench scale bioreactors have been the system of choice as the scale down model (SDM). Process characterization studies typically require a significant number of bioreactor runs, at least 4-5 rounds of 18-20 bioreactor runs, to evaluate the effect of varying multiple process parameters that could impact various critical quality attributes. Process characterization studies typically span several months and are especially resource intensive considering the number of bioreactors and an experimental duration of 2-5 weeks (fed-batch - perfusion process) per round for the production bioreactor step. In this work, we investigated high-throughput bioreactor system with 24 vessels (ambr250TM) as a SDM for fed-batch and perfusion process characterization studies. The case studies presented here illustrate the use of ambr250TM bioreactor as SDM that shows comparability with both manufacturing scale (200 – 3000 L) and bench scale (3 – 7 L) bioreactors. During the development of SDM, scale independent parameters were not altered, whereas scale-dependent parameters were scaled down according to volume ratios and scale down equipment capability. CFD (computational fluid dynamics) simulation tools were employed to study SDM mixing and their scale-up to production scale. Overall, the ambr250TM SDM met the expectations that were pre-set for the acceptance criteria both in terms of key performance indicators (KPIs) and product quality attributes (KPQAs). In addition, case studies also demonstrated the utility of ambr250TM bioreactor SDM for scale down process validation and manufacturing investigations support work (e.g. raw material lot comparisons).

High-throughput scale down model (SDM) for fed-batch and perfusion process characterization studies

253rd National Meeting (2017)

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