A novel “electrokinetic cleaning” process could let drug manufacturers recycle a greater proportion of culture media, according to researchers, who predict the approach could make perfusion-based processes more economically viable.
Perfusion bioreactors have been a mainstay of the development lab for decades. However, few firms have embraced them at commercial scale, in part, due to concerns about media costs, says Eric Wynne, PhD, a postdoctoral associate at MIT’s electronics research lab.
“While many factors have constrained adoption of perfusion bioreactors, media cost has often been cited as the main issue,” Wynne tells GEN, adding, “We believe recycling has the potential to lower costs as well as the overall volume of media involved in the manufacturing process.”
The idea, detailed in a new study, is to use a process called electrokinetic waste separation to remove cellular debris, reagents, and other potential contaminants from culture media after cultivation.
The approach uses an electric field to split media into a harvest stream that contains uncharged molecules—primarily the nutrients cells need to grow—and a waste stream in which there is a higher concentration of charged molecules, like ammonia and lactate.
“Electrokinetic waste separation provides a way of cleaning media thoroughly before recycling it. This process is what differentiates our work from previous groups that recycled media directly.
“In this work we improve the yield of this process by taking the ‘waste’ stream and processing it again to harvest additional media,” Wynne says.
The aim is to allow manufacturers to reuse a greater proportion of media—in studies, Wynne and colleagues have recovered 87.5% of spent volume—in subsequent culturing processes.
“The advantage is that, by separating waste, you can replace greater quantities of fresh media with recycled media without significantly impacting cell growth or productivity.
“Companies that use perfusion technologies already recycle media. However, typically the volume of reused media is less than 50%. Also, without a cleaning step, the reused media can negatively impact cellular growth and productivity.
“Electrokinetic waste separation has the potential to both increase the amount recycled and reduce any negative impact on productivity,” he adds.
The approach is still at a pilot stage, but the cost-saving potential is significant, particularly in combination with hybrid and fully continuous-mode manufacturing processes, Wynne says.
“More development is necessary before the technology is ready for adoption, particularly in the area of characterizing how media recycling does or does not affect product quality attributes.
“Adoption would likely require more testing at small scale and pilot scale perfusion bioreactors. Additionally, recycling and waste separation would likely be best suited for a fully continuous mAb production process with continuous chromatography downstream,” he says.
