At last month’s Bioprocessing International conference – part of Biotech Week Boston – Amgen scientist Mahsa Rohani spoke about the need for innovation in downstream continuous processes to keep up with those in the upstream when making monoclonal antibodies (mAbs).
“Recent advances in cell culture processes with increased titre and cell mass have been made in order to respond to increasing demand in monoclonal therapeutics,” she told delegates. “However, this in turn has increased the burden on clarification and downstream processes in order to remove excess solids and impurities.”
Rohani, who leads Amgen's downstream team for molecules in late stage trials, said this higher burden of solids – packed cell volume (PCV) can often reach levels greater than 15% – combined with an increased level of submicron particles exceeds the capacities of conventional harvest methods.
“It’s very difficult right now for these [monoclonal antibody] feed streams to be processed using a continuous disk-stack centrifuge [for example] and remove solids effectively without substantial loss of the product.”
She also said that with two other commonly used continuous separation technologies – depth filtration and Micro-filtration – “you are pushing the limits of floor space available in your factories.”
Therefore, she continued, “there is a great interest in biotech industry to evaluate novel harvest methods for next generation manufacturing.”
Amgen and Pall
As such, Amgen is evaluating FloDesignSonic’s Cadence Acoustic Separation (CAS) technology as a cell clarification method for monoclonal antibodies.
The technology was licensed by bioprocessing firm Pall Corporation in 2015 and has been described as a “filterless filter” which bridges the gap between the up and downstream in continuous bioprocessing.
Amgen has tested the impact of frequency, flow rate, and solid removal rate on product quality attributes (PQA) and process performance at different cell densities on four of its mAbs.
“Data from acoustic harvest trials demonstrate no impact on PQA for four different mAbs,” Rohani said.
Furthermore, Amgen found the harvest process performance improves across stages for total cell density, viable cell density and turbidity, while lowering the feed flow rate improved this further, allowing the number of filtration stages to be minimised.
Moreover, “harvest performance can be further optimised by lowering feed flow rate,” she said, though added further optimisation is required for processes with high cell density and PCV.