Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes.

Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr® 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities.

Quantitative assessment of environmental impact of biologics manufacturing using process mass intensity analysis.

Process mass intensity (PMI) is a benchmarking metric to evaluate the efficiency of a manufacturing process, which is indicative of the environmental impact of the process. Although this metric is commonly applied for small molecule manufacturing processes, it is less commonly applied to biologics. In this study, an Excel based tool developed by the ACS GCI Pharmaceutical Roundtable was used to calculate PMI of different manufacturing processes for a monoclonal antibody (mAb).

Multi-angle light scattering as a process analytical technology measuring real-time molecular weight for downstream process control.

For many protein therapeutics including monoclonal antibodies, aggregate removal process can be complex and challenging. We evaluated two different process analytical technology (PAT) applications that couple a purification unit performing preparative hydrophobic interaction chromatography (HIC) to a multi-angle light scattering (MALS) system. Using first principle measurements, the MALS detector calculates weight-average molar mass, M and can control aggregate levels in purification.