During production of monoclonal antibodies, the Protein A capture step is the first important purification step. A fast capture step is critical to retaining product integrity and processing of large feed volumes in reasonable times. Novel Periodic counter-current (PCC) processes are superior to batch processes, offering a significant economic benefit. ChromaCon’s optimized two-column PCCopt process (CaptureSMB) is the least complex and most effective PCC process allowing two-fold faster processing. It saves up to 60% of expensive Protein A resin and buffer. The Contichrom CUBE and CUBE Combined systems are process development FPLC systems employing CaptureSMB. The CaptureSMB process can seamlessly be scaled up to pilot- and process-scale with the EcoPrime Twin systems from YMC. CaptureSMB can be operated with AutomAb, a dynamic process control ensuring that any variation in fed titer or loss of dynamic binding capacity of the protein A resin over time will be compensated ensuring and maintaining optimal results during capture operation.

The CaptureSMB process is used for optimizing capture steps with affinity resins (Protein A, Ni-NTA, specific affinity resins). In batch chromatography, the column cannot be fully loaded due to the product breakthrough, and loading is stopped before reaching theoretical loading capacity to prevent product loss in the breakthrough. Breakthrough curves of single-column batch processes show that only 50-60% of the resin material is used. The CaptureSMB process operates by fully loading one column and capturing the product breakthrough on a second column (see animation below). The product is eluted from the first column, then washed and recycled and the roles of the columns are then reversed. Thus, all possible product is captured and all of the available affinity resin, for example expensive Protein A, is efficiently used.

The CaptureSMB technology is patented by ChromaCon and can be run on both the Contichrom CUBE and the Contichrom CUBE Combined. CaptureSMB processes can be created and optimized towards throughput or resin cost savings using the software wizard.

How does CaptureSMB compare to 3 or more column processes?

Capture SMB has significant advantages over multi-column processes. It operates at optimized flow rates for sub-processes, thus optimizing the overall process time and allowing flexibility in sub-processes that take fixed time allowing to use different cleaning-in-place regimes. Furthermore, it has optimized washing steps to retrieve maxium product, thereby increasing yield. CaptureSMB is better or equivalent to 3C-PCC or 4C-PCC and much better than batch, while operating at similar capacity utilization und buffer consumption. CaptureSMB, while operating with only two columns has the least complex system configuration of multicolumn systems resulting in a de-risked operation, while reaping all benefits of continuous processes. CaptureSMB has been implemented at industrial scale on Ecoprime GMP systems showing superior performance as shown in a recent publication. A virus clearance study showed that the CaptureSMB process shows an equivalent virus clearance compared to a batch process,