Cadence™ BioSMB Process System

Continuous Single-Use,
Multi-Column Chromatography
Pall’s Cadence BioSMB platform is the first disposable flow path, continuous multi-column chromatography solution that is fully scalable from the Process Development (PD) laboratory to GMP Manufacturing. The Cadence BioSMB Process system is specifically designed to allow users to convert an existing PD scale continuous purification into a process scale continuous purification based on feedstreams derived from fed batch bioreactors of up to 2000 L. The chromatographic process developed using the Cadence BioSMB PD system can be readily scaled to the Cadence BioSMB Process system without changing the sorbent, buffer system or product quality assays. BioSMB technology provides process consistency across all scales of operation while making it practical to implement in flexible, multi-product facilities.

  • Inherent unit operation efficiency of the BioSMB technology reduces the cost of chromatographic media by up to 80% without changing either the sorbent or buffer used in the chromatographic process.
  • Entire chromatographic process can be conducted in a smaller system using smaller column volumes with associated reductions in buffer that would be required in a standard batch process to produce the same amount of material.
  • The entire single-use flow path of the Cadence BioSMB Process system can be replaced within 30 minutes.
  • The valve system in the Cadence BioSMB Process system does not require cleaning or cleaning validation.
  • Ability to use up to 8 columns increases specific productivity and application flexibility.


Batch chromatographic processing typically utilizes only 50% to 70% of the chromatographic column’s total binding capacity. The Cadence BioSMB Process system, on the other hand, uses a series of interconnected and substantially smaller columns. The first column in the load zone is allowed to reach breakthrough and the product breakthrough is captured on a second column. The binding capacity of the first column can thus be exploited well beyond its batch dynamic binding capacity. In many cases, such processes can be operated close to the equilibrium or static binding capacity of the chromatographic media, thus leading to a significant reduction in chromatographic media use.

The Cadence BioSMB Process system uses continuous countercurrent loading. This requires that the load zone must only accommodate the mass transfer zone, which generally represents a small percentage of a batch column. This allows the entire process to be conducted in a much smaller system carrying only a fraction of the chromatography media used in a standard batch process. By using up to 8 smaller prepacked columns on the Cadence BioSMB Process system, the need for packing skids, large stainless steel columns, and other support infrastructure is eliminated.

While competitive systems use a complex set of valves, the Pall BioSMB technology uses an integrated valve cassette specially designed and patented as a single-use component. The new valve system eliminates the need for a difficult cleaning validation process.

The ability to use up to 8 columns with the Cadence BioSMB Process system enables a comprehensive range of capture and polishing steps such as in affinity, ion-exchange, mixed mode, hydrophobic interaction and size exclusion chromatography to be scaled up. The availability of up to 8 of columns provides a particular benefit to applications with feeds that have been concentrated and those with production titers greater than 5 g/L.

The Cadence BioSMB Process system is designed to be much more adept compared with following a simple chromatographic media optimization approach. As an example, the position of the buffer selection valves in the Cadence BioSMB Process system has been designed to contribute directly to process optimization in multiple ways. Since each column used with the Cadence BioSMB Process system is assigned a series of valves arranged in a single-use array, the result is that each pump is delivering a single fluid throughout the entire process and will never undergo composition gradients and/or wash steps. In addition, the system volume that actually is subject to composition changes in the Cadence BioSMB Process system is minimized and this eliminates many of the uncertainties associated with scale-up/scale-down, validation and process control.