Continuous Chromatography

Large and medium biopharmaceutical manufacturers and contract development and manufacturing organizations (CDMO) are seeking to increase productivity with a smaller footprint and with challenging modalities for their multi-product facilities, resin cost & buffer consumption, start-up and change-over times, and labor cost, in general, are becoming critical.

Continuous and connected systems based on Single-Use technologies should enable a scaled-down facility for both clinical and commercial operations. Complete Single-Use technology implementation in combination with continuous operation will lead the Biopharma industry to full flex Multi-Product Facilities. Scaling out instead of scaling up for simplified and tighter control with reduced risk of bioburden and deviations. 

  • Seamless scalability from PD to commercial manufacturing 
  • Approx. 3-5-fold increase in productivity with up to 80% savings on chromatography media and associated costs at capture step 
  • Proprietary, easy to install single-use manifolds greatly reduces the risk of cross contamination 
  • Industry preferred single-use based multicolumn chromatography (MCC) skid for perfusion and batch-based processes 
  • Modular design and flexible column arrangement (series or parallel) 
  • Single use cassettes and flow path 


Find the Right Solution for Your Chromatography Process

The BioSMB platform is fully scalable from process development (PD) to commercial manufacture. There are two flow range variants available targeted to perfusion (BioSMB Process 80 system) and batch (BioSMB Process 350 system) bioreactor-based processes. 
Attributes BIOSMB PD BIOSMB Process 80/350
Description  Only MCC system that makes 24 hour process development a reality  Designed for (conc.) fed-batch and perfusion applications with a single- use flow path that can be set up in 30 min or less 
Scale of operation Process Development and Small-Scale Manufacturing Clincal and Commercial Manufacturing 
Number of Columns  3-16 3-8
Flow Rate Range  0.6 – 8 L/hr  5 – 80 L/hr for BIOSMB 80 
30-350 L/hr for BIOSMB 350 
Learn More Learn More


BioSMB PD is an integrated single-use device for process development to fully automate a wide variety of chromatographic processes, including bind/elute chromatography and flow-through polishing. 


Continuous Single-Use,
Multi-Column Chromatography

The 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 BioSMB system is specifically designed to allow users to convert an existing batch process into a continuous chromatography step without changing the chromatographic separation media, buffer system or product quality assays. BioSMB technology provides process consistency across all scales – development, clinical and full production – and is also practical to implement in flexible, multi-product facilities.

  • Inherent unit operation efficiency of the BioSMB PD system reduces the cost of chromatographic media by up to 80% without changing either the separation media or buffer used in the chromatographic process.
  • Entire chromatographic process can be conducted in a smaller system containing a fraction of the media and buffer that would be required in a standard batch process to produce the same amount of material.
  • Ability to use up to 16 columns increases specific productivity and application flexibility. Position of the buffer selection valve eliminates composition gradients and wash steps.


Batch chromatographic processing typically utilizes only 50% to 70% of the chromatographic column’s total binding capacity. The BioSMB PD system, on the other hand, uses a series of substantially smaller, interconnected 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 BioSMB PD system use of continuous countercurrent loading means that the load zone must accommodate only 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. When used in larger scale applications, BioSMB technology can eliminate the need for packing skids, large stainless steel columns, and other support infrastructure. This results in a smaller overall footprint and a more scalable configuration.

While competitive systems use a complex set of valves, the 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 16 columns with BioSMB PD system means that it supports the broader application base of capture and polishing steps such as in HIC, SEC, mixed mode chromatography, as well as combinations of these technologies. The availability of a greater number of columns provides a particular benefit to applications with feeds that have been concentrated and those with production titers greater than 5 g/L.

Compared with competing systems, the BioSMB system is designed to offer far greater capabilities than those that can be provided by simple chromatographic media utilization optimization. As an example, the position of the buffer selection valves in the BioSMB PD system is very different from other systems and contributes directly to process optimization in multiple ways. Because each column used with the BioSMB PD system is assigned a series of valves arranged in a single-use array, the result is that every pump is delivering one buffer 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 BioSMB PD system is minimized well beyond that of other system designs. This eliminates many of the uncertainties associated with scale-up/scale-down, validation and process control.



Cadence BioSMB PD technology is the ideal solution for biopharmaceutical production applications ranging from early stage process development through clinical manufacture and beyond. This integrated single-use device contains all the valves necessary to fully automate a wide variety of chromatographic processes including bind/elute chromatography (Protein A affinity, ion exchange, mixed mode, hydrophobic interaction) and flow through such as size exclusion or ion exchange polishing. It provides an open platform for downstream processing that enables the use of any separation technology including packed bed chromatography, membrane chromatography, monoliths, and expanded bed adsorption (EBA) chromatography.


General Specifications

Width / Depth / Height

120 / 73 / 58 cm (47.2 / 28.7 / 22.8 in.)


170 kg (375 lbs)

Electrical Requirements

115 V or 230 V

Required Air Supply

At least 1 barg (14.5 psig) above process pressure

System and Valve Cassette Specifications

Flow Rate Range

1 mm cassette: Up to 50 mL/min
3 mm cassette: Up to 100 mL/min


Maximum 8 (including loopback)


Maximum 6 (including loopback)


Maximum 16

Maximum Operating Pressure

10 barg (145 psig)

Sensor Specifications


Linear up to 13.8 barg (200 psig)

Ultraviolet-Visible (UV-VIS)

Four UV-VIS sensors each with wavelengths in 210-850 nm range


Maximum 8 Range of 0-14, accuracy of 0.1 pH unit (from 2 to 12)


Range: 1 μS/cm – 200 mS/cm
Accuracy: 0.25 mS/cm (range 10 – 200 mS/cm) 3.0 μS/cm (range 0 – 100 μS/cm)

Pump Specifications

Maximum of 7 pumps
Stepper motor belt drive dual piston pumps, PEEK fluid path, automated piston seal wash, double capsule check valve with additional anti-siphoning valve


0.5 – 50 mL/min ± 5% (with 1 mm cassette)
0.5 – 100 mL/min ± 5% (with 3 mm cassette)

Ordering Information

Part Number Description
BIOSMB-PD-LD100 BioSMB PD 1 mm Process Development System
BIOSMB-VC-1 BioSMB PD 1 mm Process Development Valve Cassette only
BIOSMB-VC-3 BioSMB PD 3 mm Process Development Valve Cassette only
BIOSMB-PW-200 Pump wash kit 1-200 mL/min
BIOSMB-TK-1A 1 mm tubing kit – LD100 pumps ONLY with 1 mm cassette
BIOSMB-TK-3A 3 mm tubing kit – LD100 pumps ONLY with 3 mm cassette
BIOSMB-PH-1 BioSMB pH housing for 1 mm setup
BIOSMB-PT-1 BioSMB pressure transducer
BIOSMB-COND BioSMB conductivity sensor
BIOSMB-UV-1S BioSMB UV flow cell, 2.5 mm optical path
BIOSMB-UV-1L BioSMB UV flow cell, 10 mm optical path
BIOSMB-PD-CH Pack of column holders
Request a Quote

BIOSMB Process 80/350

Single-Use BioSMB is the core differentiator in the toolbox for intensified chromatography, by processing a bioreactor batch or effectively connecting with upstream and providing continuous capture and polishing chromatography in downstream, resulting in full-media-utilization at smaller footprint and reduced operational cost and risk.    

BioSMB technology can eliminate the need for packing skids, large stainless steel columns, and other support infrastructure. This results in a smaller overall footprint and a more scalable configuration. 


Single-Use Continuous Chromatography Systems For Perfusion and Batch Bioreactor-based Processes

The BioSMB platform provides a highly flexible multicolumn chromatography system that delivers high throughput and very efficient media utilization when compared to traditional batch, and other continuous chromatography methodologies. This is achieved through a unique single-use eight column system architecture which enables a highly flexible flow configuration through the single-use valve cassette. Additionally, the platform is fully scalable from process development (PD) to commercial manufacture. There are two flow range variants available targeted to perfusion (BioSMB Process 80 system) and batch (BioSMB Process 350 system) bioreactor-based processes.

Chromatographic processes developed using batch chromatography can be readily scaled without changing the sorbent, buffer system or product quality assays.

Benefits include:

  • Highly efficient sorbent utilization
  • High productivity
  • Unparalleled flexibility
  • Less than 30 minute manifold installation

By using up to eight smaller pre-packed columns on the BioSMB Process systems, the need for column packing skids, large columns, and other support infrastructure is eliminated.

BioSMB Continuous Chromatography System

1. Separation Media Utilization

Batch chromatographic processing typically utilizes only 50% to 70% of available binding capacity in the column. To maximize the use of the available binding capacity the BioSMB platform provides the ability to overload a given column, with the breakthrough passed directly onto a subsequent column.

Key benefits:

  • Column capacity is maximized
  • Buffer consumption is optimized through improved sorbent utilization

The separation media utilization benefits can be leveraged to optimize the purification strategy, i.e. run at a shorter residence time than batch but achieve a similar operational binding capacity – increasing productivity (a typical BioSMB strategy for clinical material production). Alternatively the process can be run at a flow rate similar to that used in a batch process with greatly increased operational binding capacity.

2. Achieving Higher Throughput

Essential to the process economics of the BioSMB platform is the availability of multiple columns for continuous loading. Typically the bottleneck in high titer chromatography is the non-load operations. In batch and two column designs, loading cannot be repeated until the non-load steps are completed. With the BioSMB systems the process can be configured such that the loading steps are continuous; there is always a column ready to be loaded – this often requires a minimum of four columns.

The BioSMB Process platform has the ability to process on up to eight columns.

3. Flexibility

Furthermore, the flexibility of the valve cassette allows multiple columns to be available in the breakthrough zone to collect overload from one column and wash from another, meaning flow rates can be kept high and constant without exceeding the maximum linear velocity for the columns; further increasing productivity.

4. Valve Cassette

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

Each column used with the BioSMB Process systems is assigned a series of valves arranged in a dedicated array, resulting in each pump delivering a single fluid throughout the entire process and eliminating gradients or wash steps between buffer switches.

Additionally, throughout the BioSMB product range, the system hold-up volume is minimized, eliminating many of the uncertainties associated with scaling, validation and process control.

5. Scale Up and Scale Down

To complement the BioSMB Process 80 and BioSMB Process 350 systems, a bench scale version is available, the BioSMB PD system.

The BioSMB PD system uses the same valve technology, flow path configuration and recipe handling to ensure simple scale-down or scale-up. This system is available for flow rates up to 100 mL/min.


The BioSMB Process 80 and 350 systems are the ideal solution for manufacturing-scale continuous chromatography.

BioSMB Process 80 System for Perfusion Bioreactor-Based Processes

The BioSMB Process 80 system, when coupled with the BioSMB Process 80 perfusion manifold, is targeted for perfusion bioreactor-based processes that will run for longer periods of time. The flow rate capability along with the specifically designed low bio-burden manifold meet the requirements for lower flow continuous processing.

BioSMB Process 350 System for Batch Bioreactor-Based Processes

The BioSMB 350 system is targeted for batch bioreactor-based processes up to 2000 L. The flow rate capability and larger bore single use tubing, and cassette manifold meet the requirements for high throughput continuous processing.


The software is designed to provide the operator a clear and easy-to-use interface. It has been developed in accordance with usability standards for the most efficient, error-free user experience.


BioSMB Process 80 and 350 Complete Hardware Systems

Each BioSMB Process 80 and 350 system has the following architecture

2.7/1.3/2.1 m (106/51/83 in.)
Height without alarm tower: 1.9 m (75 in.)
Flow Rate Range PROCESS 350 30-350 L/h
Flow Rate Range PROCESS 80 5 – 80 L/h
Weight 1000 kg
Inlets 8 (7 usable + 1 for system use as second pass)
Outlets 6 (5 usable + 1 for system use as second pass)
Number of column
Number of pumps 7
Maximum operating
4 bar (58 psi)
Air supply 6 bar (87 psi) with integrated pressure regulator
Electricity supply 3 phase 400 V – 32 A – 50 Hz
(other voltages available)

BioSMB Pump Modules

If a complete BioSMB Process 80 or Process 350 system is purchased, then it is possible to buy a BioSMB Process 80 or Process 350 pump module respectively to increase the flexibility of the main system.

The pump module can be exchanged easily, requiring a mechanical changeout of the module and a switch in the software. The mechanical swap of the two pump modules typically takes less than an hour. This modularity allows the system to run either from 5 L/h – 80 L/h (BioSMB Process 80 pump module) or 30 – 350 L/h (BioSMB Process 350 pump module).

If a BioSMB Process 80 pump module is used then the BioSMB Process 80 manifold set must be used, and if a BioSMB Process 350 module is used then a BioSMB Process 350 manifold set must be used.

BioSMB Process 80 and 350 Platform – Single-Use (SU) System   

Manifold specifications

Item Description
Hose and connectors
process 350
Silicone braided tubing ID: ⅜ in. with
HFC39 connectors for internal connections
and sanitary connection clamp 3/4 in. for upstream and
downstream connections
Hose and connectors
process 80
Silicone braided tubing ID: 1/4 in. Kleenpak®
Presto sterile connector for external connections.
HFC39 connectors for internal connections
(NOTE: The process 80 manifold is available
with sanitary connection connections in place of the
Kleenpak connectors. Contact Pall for more details)
Pressure 7 pressure transmitters (1 after each pump with
integrated pressure switch)
0 to 5 barg/72 psig
(NOTE: Maximum operating pressure for system
is 4 barg/58 psig)
Flow 7 ultrasonic non-invasive flowmeters
(1 after each pump)
Air 7 integrated with flowmeters
Conductivity 4 sensors (on outlets 1-4)
Range: 0 μS/cm – 150 mS/cm,
accuracy of 2% measuring range
Built in temperature compensation
and monitoring.
pH 4 sensors (on outlets 1-4) Range of 2-10,
accuracy of 0.15 pH unit
UV 4 UV-VIS sensors each with wavelengths in
280 nm as standard
0-2 AU
Process pump 4 piston diaphragm single-use
The single-use pump heads are Quattroflow™
sanitary diaphragm pumps, 4 pistons with
polypropylene (PP), ethylene propylene diene
monomer (EPDM)/PP compound diaphragm
and EPDM valves
Gamma irradiation dose 25 kGy

Process wetted components materials of construction

Description Materials
Tube Platinum cured silicone
Fittings Polycarbonate, polypropylene, polyphenylsulfone
Valve diaphragm Fluoroelastomer (FKM)
pH sensor Glass
Pump head Polypropylene, EPDM/PP compound
Pressure sensor Polysulfone
UV-VIS sensor windows Quartz
Conductivity sensor Polysulfone

Ordering Information