Interview with Dr Jack Cordrey
Resin-based chromatography is still used today for a lot of downstream polishing processes of monoclonal antibodies and other biomolecules. However, it is a costly and time-consuming process, especially when accounting for high packing failure rates and the necessity for cleaning and sterilisation after each use. Next generation membrane adsorbers like 3MTM Polisher ST that can replace resin-based polishing chromatography are offering a lot of advantages like higher recovery, lower costs, easier handling and better sustainability, all inside a single use, flow through device. Dr Jack Cordrey, Bioprocess Applications Specialist of 3M explains.
“Our membrane adsorber 3M™ Polisher ST can do three steps of the downstream purification of monoclonal antibodies (mAbs) in one”, he says. “That really makes a difference in product recovery and cost of goods etc.” Polisher ST is a single use device that has been on the market since 2021. “We’ve had a lot of interest from people working at lab scale but also in scaling up processes for all of their biomolecules of interest. Slowly more and more people are integrating it in their system. However, column-based chromatography is still used by the majority of clients at commercial manufacturing scale. It has been around for decades, so it is familiar to most people and they feel comfortable with it. Adopting a new technique takes time for people and companies, especially in the highly regulated pharmaceutical world,” says Cordrey.
Three steps in one
After the viral inactivation process post capture chromatography in mAb purification, usually a depth filter is used, followed by a sterilising grade membrane and then anywhere between one to three polishing resin chromatographic columns. These last three steps can be replaced by the 3M™ Polisher ST membrane adsorber utilizing its bio-inspired guanidinium functionalized membrane paired with a Q-functional media for improved process robustness to handle feed variation and turbidity and high performance across a wide range of pH and conductivity conditions. Following the use of Polisher ST only a single polishing column is required to deal with any remaining product-related impurities.
High product yield, lower costs
Data from clients who have already adopted the 3M™ Polisher ST in their processes and internal process modelling have shown product recovery increases, costs of goods decreases, and improved process sustainability. To give some data: from bioreactor all the way to the mAb end product using a traditional process with polishing resin chromatography the typical recovery is 52%. Replacing the aforementioned three steps with 3M™ Polisher ST the recovery can be increased to 62%. Cordrey: “That may not sound like much but familiarize yourself with a manufacturing scenario using the traditional approach where you need to run ten batches to get your product quantity. With the gains from using Polisher ST, based on product recovery, you only need to run nine batches, saving significant costs in production and resources such as like water, buffers, etc. It’s a lot more sustainable, since there is a significant (10-20%) reduction in process mass intensity (PMI), the total mass of reagents needed per mass of product. The costs of goods per gram of mAb also decreases: from 138-140 USD using the traditional technique to 108-110 USD with Polisher ST (at a scale of 6 x 1800 litres of fluid). Furthermore, since it’s a single use device, column cleaning, sterilization and packing are no longer necessary which saves a lot of time.”
Robustness
One of the key benefits of the 3M™ Polisher ST compared to other next generation adsorbers is its robustness in performance. It can deal with high salt conditions, turbidity, larger pH ranges and multi-valent buffers and still give higher performance, which allows operating it in a wider range of conditions. This is all credit to its dual anion-exchange architecture with a Q-functional non-woven mounted onto a bio-inspired guanidinium membrane.
Dr Jack Cordrey gave this interview before his lecture at the Single-Use Event 2022