Cadence™ BioSMB Process System product photo Primary L

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.

Benefits

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.



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Description
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.

Benefits

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.

Applications

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

Cadence BioSMB Process 80 System for Perfusion Bioreactor-Based Processes

The Cadence BioSMB Process 80 system, when coupled with the Cadence 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.

Cadence BioSMB Process 350 System for Batch Bioreactor-Based Processes

The Cadence 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.

Software

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

Figure 1 Example - Cadence BioSMB software

The Cadence BioSMB software allows users to create methods either on the system directly or remotely on another PC (using another install) which can then be downloaded to the Cadence BioSMB Process 80 and Process 350 systems.

The software uses a proprietary visualization tool called the circular chronogram (Figure 2). The circular chronogram allows users to know the exact position of the columns within a process cycle at any given time.

Figure 2 Cadence BioSMB Process 350 circular chronogram

Methods developed on the Cadence BioSMB PD system, using up to eight columns, are directly transferable to the Cadence BioSMB Process 350 system.

Specifications

Cadence BioSMB Process 80 and 350 Complete Hardware Systems




Table 1
Each Cadence BioSMB Process 80 and 350 system has the following architecture
 
Dimensions
w/d/h
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
positions
8
Number of pumps 7
Maximum operating
pressure
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)
 

Cadence BioSMB Pump Modules

If a complete Cadence BioSMB Process 80 or Process 350 system is purchased, then it is possible to buy a Cadence 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 (Cadence BioSMB Process 80 pump module) or 30 - 350 L/h (Cadence BioSMB Process 350 pump module).

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

Figure 3 Cadence BioSMB Process 80 pump module

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

Table 2
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
 

Table 3
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
 
Additional Information

Continuous Biomanufacturing Implementation Now and in the Future



Ordering Information

Cadence BioSMB Process 350 SU Systems

Table 4

The Cadence BioSMB Process 350 SU system is comprised of four separate manifolds; inlet manifold, valve cassette manifold, column manifold and outlet manifold. These can be purchased individually, the manifolds are supplied individually double bagged and gamma irradiated.

 
Part Number Description
BIOSMB-IT-8 Cadence BioSMB Process 350 inlet tubing set
BIOSMB-OT-8 Cadence BioSMB Process 350 outlet tubing set
BIOSMB-CT-8 Cadence BioSMB Process 350 column tubing set
BIOSMB-VB-8 Cadence BioSMB 8 mm Process 350 valve cassette
 

Figure 4
Cadence BioSMB Process 350 SU system manifold

*Second pass and column tubing not shown.

Cadence BioSMB Process 80 SU Systems

Table 5

The Cadence BioSMB Process 80 SU system is comprised of one single manifold. The system is supplied double bagged and gamma irradiated.

 
Part Number Description
BIOSMB-PF-5 Cadence BioSMB Process 80 SU system
comprising inlets, valve cassette, outlets and
column connectors only. Other connectors are
available on request.
 
Figure 5 Cadence BioSMB Process 80 SU system manifold