USD 2706

CadenceTM Single-pass Tangential FlowFiltration Modules and Systems

Single-pass TFF is a breakthrough technology thatallows direct flow-through concentration with norecirculation of product. This exciting new technologyleads to economic and practical benefits, including:

Increased yield of product due to improvedrecovery capability and lower hold-up volume.

Increased final product concentration due to high concentration factor capability.

Elimination of product damage or aggregationdue to reduced residence time and shear exposure.

Ability to couple the concentration of productbefore 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 chromatographyor 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.

Eliminate the recirculation loop and streamline operations to optimize downstream processing

Optimize Economic and Operational BenefitsEnhance downstream processing to increasecapacity 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 ofthe 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 thestaging of cassettes in series, which results in highconversions of feed-to-permeate in one flow path. This is accomplished by optimizing the module stagingconfiguration based on cassette performance for aparticular application.

Optimize processing of highly shear-sensitiveproducts – Processing results in only one pass throughthe pump and cassette, reducing shear exposure. For products sensitive to pumping, the pump can becompletely eliminated by using pressurized vessels toflow the process fluid through the module. Furtherbenefits are achieved by eliminating any mixing orfoaming issues associated with the feed tank.

Use smaller, more compact systems – Cadencesystems require less pump capacity, allowing smallerpiping or tubing diameters for a more compact systemdesign with lower working and hold-up volumes.

Simplify installation and use – Cadence modules aresupplied preassembled. The modules’ feed, retentate and permeate ports are easily connected to clearly-marked system ports.

ApplicationsCadence single-pass TFF modules and systems are used to concentrate biomolecules. They also can be used forsalt-level reduction by concentrating followed by in-linedilution. Volume capacities range from several liters tothousands of liters. Single-pass TFF may be used toperform various steps in a wide range of applicationsin 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-designedCadence system. Contact Pall for more information on single-use systems.

Product PlatformInnovative single-pass TFF processing takes place within Cadence modules. Cadence modules incorporatePall’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 Cadencesingle-pass TFF system. (Contact Pall for information on aCadence system to meet your application requirements.)

Cadence T01 Module Installed in Holder

www.pall.com/biopharm

Cadence Modules Incorporate High PerformanceT-Series Cassettes with Delta MembraneDelta regenerated cellulose membrane offers high flux andselectivity. The membrane has been specifically developedto minimize protein binding to the surface and interstitialstructure 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 foulingcharacteristics, allowing consistent performance or flux from run to run. It is easy to clean and typically recoversnormalized water permeability (NWP) by using 0.1 N NaOH.

SpecificationsThe operating conditions and module configurations for anysingle-pass TFF process must be established by performingtrials and analyzing results. Pall’s Technical Support Group isavailable to assist in conducting trials to select configurationsand develop operating conditions necessary to achieve thedesired process objectives.

Cadence Module Materials of Construction

Membrane Delta regenerated cellulose, 10 kDSupport Polypropylene Screens Polypropylene Encapsulant Polyurethane with white pigment (TiO2)Permeate Seals Medical grade, platinum cured siliconeGaskets Medical grade, platinum cured silicone

Cadence Module Operating Limits

Maximum Pressure 6 barg (87 psig) @ 23 °C4.1 barg (60 psig) @ 55 °C

Maximum Transmembrane 4.1 barg (60 psig) @ 4 – 55 °CPressure (TMP)Processing Temperature Range 4 – 40 °C

(freezing will damage module)pH Range 2 – 13Flow Rate Range During Cleaning < 2 L/min/m2 (0.2 L/min/ft2)

Cadence Module Typical Feed Flow Rates in L/min/m2 Concentration Factor

Process Flux* 4X 10X 30X10 LMH 0.22 0.19 0.1750 LMH 1.11 0.93 0.86100 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 < 0.07 barg (1 psig) per minute(System)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 preservativeis expected to be three years from the date of manufacturewhen the modules are stored unopened in the originalpackaging at temperature 4 – 25 °C and protected fromdirect light. Extended shelf life studies are ongoing.

Biological Safety

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

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

Flu

x (L

MH

)

25

20

15

10

5

0 100 1000

Concentration (g/L)

Final Retentate Concentration = 252.4 g/L

Overall Flux

T-Series Cassettes in Cadence T01 Module

DocumentationEach 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

Ordering InformationIdentify 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 partnumber CD010T010815. Note: a Pall Cadence system must beused to operate Cadence modules. (Contact Pall for informationon a Cadence system to meet your application requirements.)

Guide to Cadence Module Part NumbersC D 010 T01 08 15Concentration Delta membrane Nominal molecular Cassette format Number of cassettes Total number of

weight cutoff (10 kD) in series cassettes in moduleExample: Part number CD010T010815

Delta 10 kD Cadence Module Membrane Area (m2) Part NumberT01 0.12 CD 010 T010713T01 0.14 CD 010 T010815T01 0.17 CD 010 T010918T02 0.24 CD 010 T020713T02 0.28 CD 010 T020815T02 0.33 CD 010 T020918T12 1.3 CD 010 T120713T12 1.5 CD 010 T120815T12 1.8 CD 010 T120918

Europe+41 (0)26 350 53 00 phone+41 (0)26 350 53 53 faxLifeSciences.EU@pall.com E-mail

United States1.800.717.7255 toll free (USA)1.516.484.5400 phone1.516.801.9548 faxbiopharm@pall.com E-mail

International OfficesPall Corporation has offices and plants throughout the world in locations such as: Argentina, Australia, Austria,Belgium, Brazil, Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico,the Netherlands, New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden,Switzerland, Taiwan, Thailand, the United Kingdom, the United States, and Venezuela. Distributors in all major industrial areas of the world.

The information provided in this literature was reviewed for accuracy at the time of publication. Product data may besubject to change without notice. For current information consult your local Pall distributor or contact Pall directly.

© 2010, Pall Corporation. Pall, and Cadence are trademarks of Pall Corporation. ® indicates a trademarkregistered in the USA and TM indicates a common law trademark. Filtration. Separation. Solution.SM is a servicemark of Pall Corporation.

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