Cadence™ Single-Pass Tangential Flow Filtration Modules and Systems

Eliminate the Recirculation Loop and Streamline Operations to Optimize Downstream Processing

Single-pass TFF is a breakthrough technology that allows direct flow-through concentration with no recirculation of product. This exciting new technology leads to economic and practical benefits, including:

• Increased yield of product due to improved recovery capability and lower hold-up volume.
• Increased final product concentration due to high concentration factor capability.
• Elimination of product damage or aggregation due to reduced residence time and shear exposure.
• Ability to couple the concentration of product before or after other downstream process steps, consequently optimizing other steps and reducing in-process pool tank volumes.
• Available in single use format and system design.

Cadence single-pass TFF modules and systems can be easily integrated with other downstream processes such as chromatography or virus removal. 

Using Cadence modules with Delta membrane, the innovative benefits of single-pass TFF technology are enhanced by the proven high flux, high selectivity, and low protein binding attributes of Delta regenerated cellulose membrane.

Optimize Economic and Operational Benefits

• Enhance downstream processing to increase capacity and reduce costs – Cadence systems can eliminate or reduce intermediate storage tanks and associated cleaning of tanks when using the systems for in-process volume reduction before or after existing steps.
• Increase yield and achieve high product recovery > 98 % – The single-pass TFF process collects most of the process volume during the process run, leaving only a small percentage of the product in the module at the end of the run. This small percentage of product can be easily recovered due to the low hold-up volume in the system.
• Enable high concentration factors > 20X – High concentration factors are achieved due to the staging of cassettes in series, which results in high conversions of feed-to-permeate in one flow path. This is accomplished by optimizing the module staging configuration based on cassette performance for a particular application.
• Optimize processing of highly shear-sensitive products – Processing results in only one pass through the pump and cassette, reducing shear exposure. For products sensitive to pumping, the pump can be completely eliminated by using pressurized vessels to flow the process fluid through the module. Further benefits are achieved by eliminating any mixing or foaming issues associated with the feed tank.
• Use smaller, more compact systems – Cadence systems require less pump capacity, allowing smaller piping or tubing diameters for a more compact system design with lower working and hold-up volumes.
• Simplify installation and use – Cadence modules are supplied preassembled. The modules’ feed, retentate and permeate ports are easily connected to clearly-marked system ports.

Product Platform

Innovative single-pass TFF processing takes place within Cadence modules. Cadence modules incorporate Pall’s proven T-Series cassettes with Delta membrane, and are available in different sizes to accommodate various processing volumes (see Ordering Information). Cadence modules are designed for use with a Pall Cadence single-pass TFF system. (Contact Pall for information on a Cadence system to meet your application requirements.)

Cadence Modules Incorporate High Performance T-Series Cassettes with Delta Membrane

Delta regenerated cellulose membrane offers high flux and selectivity. The membrane has been specifically developed to minimize protein binding to the surface and interstitial structure of the membrane. Inherently hydrophilic, this membrane shows low protein adsorption properties and is optimal for processes involving very hydrophilic proteins. Delta regenerated cellulose membrane shows low fouling characteristics, allowing consistent performance or flux from run to run. It is easy to clean and typically recovers normalized water permeability (NWP) by using 0.1 N NaOH.

Cadence T01 Module Installed in Holder

Cadence single-pass TFF modules and systems are used to concentrate biomolecules. They also can be used for salt-level reduction by concentrating followed by in-line dilution. Volume capacities range from several liters to thousands of liters. Single-pass TFF may be used to perform various steps in a wide range of applications in the biopharmaceutical industry, including:

• In-process volume reduction
• Desalting protein solutions
• Purification and recovery of antibodies or recombinant proteins
• Preparation of samples (concentrating, desalting) before or after column chromatography

Single-Use Applications

Depending on the application, Cadence modules may also be applied for single use. When applied for single use, Cadence modules are used with a specially-designed Cadence system. Contact Pall for more information on single-use systems.

The operating conditions and module configurations for any single-pass TFF process must be established by performing trials and analyzing results. Pall’s Technical Support Group is available to assist in conducting trials to select configurations and develop operating conditions necessary to achieve the desired process objectives.

Cadence Module Materials of Construction
Membrane	Delta regenerated cellulose, 10 kD and 30 kD
Support	Polypropylene
Screens	Polypropylene
Encapsulant	Polyurethane with white pigment (TiO2)
Permeate Seals	Medical grade, platinum cured silicone
Gaskets	Medical grade, platinum cured silicone

Cadence Module Operating Limits
Maximum Pressure	6 barg (87 psig) @ 23 °C 4.1 barg (60 psig) @ 55 °C
Maximum Transmembrane Pressure (TMP)	4.1 barg (60 psig) @ 4 - 55 °C
Processing Temperature Range	4 to 40 °C (freezing will damage module)
pH Range	2 to 13
Flow Rate Range During Cleaning	< 5 L/min/m2 (0.2 L/min/ft2)

The performance of Cadence modules, based on an IgG model feed solution, is demonstrated in the table below over a wide range of feed flow rates (L/min/m²) and volumetric concentration factors (X) for various module configurations and feed concentrations (g/L).

Cadence Module Typical Feed Flow Rates in L/min/m2	Concentration Factor
Process Flux*	4X	10X	30X
10 LMH	0.22	0.19	0.17
50 LMH	1.11	0.93	0.86
100 LMH	2.22	1.85	1.72

* LMH = Liters/meter²/hour

Cadence Module Integrity Test
Systems Integrity Test Pressure	4.1 barg (60 psig)
Acceptable Pressure Decay (System)	< 0.07 barg (1 psig) per minute
Module Integrity Test Pressure	4.1 barg (60 psig)
Acceptable Forward Flow Rate	< 50 sccm/ft2 (538 sccm/m2)

Each Cadence module has a unique serial number for full traceability.

Shelf Life

The shelf life of Cadence modules packaged in preservative is expected to be three years from the date of manufacture when the modules are stored unopened in the original packaging at temperature 4 – 25 °C and protected from direct light. Extended shelf life studies are ongoing.

Biological Safety

Materials of construction for Cadence modules have been tested and meet the requirements for the Biological Reactivity Tests listed in the United States Pharmacopeia (USP) under USP <88> for Class VI - 70 °C Plastics.

Documentation

Each module is supplied with the following comprehensive documentation to ensure the Cadence module is operated successfully:

• Certificate of Quality
• Care and Use Procedures
• Material Safety Data Sheet for the module preservative

Contact your local Pall representative to obtain:

• Validation Guide
• Validation service for specific tests such as compatibility testing with your product fluid
• Training and technical support to optimize your process using Cadence systems

Pall Provides Comprehensive Documentation with Each Cadence Module

Achieve High Concentration Factors:
Flux Versus Concentration for Cadence Modules with Delta 30 kD Membrane
MAb Material (53.2 g/L Initial Concentration)

• Cadence Systems Employ New Single-Pass TFF Technology to
  Simplify Processes and Lower Costs 

Identify

and order Cadence modules using the table below. For example, a Cadence T01 module with 10 kD Delta regenerated cellulose membrane area of 0.14 m² (1.5 ft²) is part number CD010T010815. Note: a Pall Cadence system must be used to operate Cadence modules. (Contact Pall for information on a Cadence system to meet your application requirements.)

Guide to Cadence Module Part Numbers

Example: Part number CD010T010815

C	D	010	T01	08	15
Concentration	Delta membrane	Nominal molecular weight cutoff (10 kD)	Cassette format	Number of cassettes in series	Total number of cassettes in module

Cadence Module	Configuration	Delta 10 kD Membrane Area (m2)	Part Number
T01	4-in-series	0.065	CD 010 T010407
T01	7-in-series	0.12	CD 010 T010713
T01	8-in-series	0.14	CD 010 T010815
T01	9-in-series	0.17	CD 010 T010918
T02	4-in-series	0.13	CD 010 T020407
T02	7-in-series	0.24	CD 010 T020713
T02	8-in-series	0.28	CD 010 T020815
T02	9-in-series	0.33	CD 010 T020918
T12	4-in-series	0.7	CD 010 T120407
T12	7-in-series	1.3	CD 010 T120713
T12	8-in-series	1.5	CD 010 T120815
T12	9-in-series	1.8	CD 010 T120918
T06	4-in-series	3.5	CD 010 T060407
T06	7-in-series	6.5	CD 010 T060713
T06	8-in-series	7.5	CD 010 T060815
T06	9-in-series	9.0	CD 010 T060918
Cadence Module	Configuration	Delta 30 kD Membrane Area (m2)	Part Number
T01	4-in-series	0.065	CD 030 T010407
T01	7-in-series	0.12	CD 030 T010713
T01	8-in-series	0.14	CD 030 T010815
T01	9-in-series	0.17	CD 030 T010918
T02	4-in-series	0.13	CD 030 T020407
T02	7-in-series	0.24	CD 030 T020713
T02	8-in-series	0.28	CD 030 T020815
T02	9-in-series	0.33	CD 030 T020918
T12	4-in-series	0.7	CD 030 T120407
T12	7-in-series	1.3	CD 030 T120713
T12	8-in-series	1.5	CD 030 T120815
T12	9-in-series	1.8	CD 030 T120918
T06	4-in-series	3.5	CD 030 T060407
T06	7-in-series	6.5	CD 030 T060713
T06	8-in-series	7.5	CD 030 T060815
T06	9-in-series	9.0	CD 030 T060918