Comparison of process mass intensity (PMI) of continuous and batch manufacturing processes for biologics.

Biologics encompasses a wide variety of therapeutics including monoclonal antibodies, fusion proteins, and enzymes, among others. The biologics market is growing at a rapid pace and different manufacturing processes, including continuous manufacturing processes, are being increasingly adopted. There is a strong drive to assess the sustainability of such processes. Here, we calculated the process mass intensity (PMI) of a continuous manufacturing process and compared it to the PMI of batch processes for monoclonal antibodies (mAbs). Results show that the PMI of continuous manufacturing process is comparable to that of batch processes. Sensitivity analysis was performed to assess the impact of different process strategies on the material usage efficiency of continuous processes. Although PMI is a useful benchmarking metric of sustainability, it does not account for factors such as energy consumption which is a key driver of sustainability for biologics manufacturing. Comparison of a higher PMI continuous process with a lower PMI batch process operating at the same bioreactor scale shows that since the productivity (in g of drug substance, DS) per unit time is multifold higher for the continuous process, the overall energy consumption per unit of DS produced might be lower leading to a more environmentally sustainable process. This study highlights some of these key aspects that would require additional metrics and models to be developed to assess the overall sustainability of biologics processes.