Single-pass continuous diafiltration made simpler with Delta 30 kDa regenerated cellulose and Omega™ 30 kDa PES membrane
Single-pass tangential flow filtration (SPTFF) has revolutionized the implementation of TFF in biotech, vaccine, blood plasma and other applications. The Cadence inline diafiltration (ILDF) device addresses a gap in the biopharmaceutical industry, by completing the product/technology offering for the realization of continuous processing of the final ultrafiltration/diafiltration (UF/DF) of drug substance. The Cadence ILDF module moves the biopharm industry one step closer to an end-to-end integrated continuous bioprocessing platform.
This latest addition to the Pall portfolio has many benefits, including:
- Fully continuous diafiltration in the downstream processing (DSP) steps
- Significantly reduced system hold-up volume
- Easy to use, holderless design
- Potential reduction of product damage or aggregation due to reduced residence time and shear exposure
Cadence inline diafiltration modules are preassembled and do not require a holder. Each device includes a pre-configured tubing set that is connected to a feed pump and a diafiltration buffer pump. Torque the module to the recommended setting and it is ready to operate.
The Cadence ILDF technology allows for removal factors of ≥ 3-log. Utilizing conventional TFF cassette building blocks in either Delta regenerated cellulose or Omega polyethersulfone membrane ensures accurate scalability and proven selectivity, and low protein binding attributes.
These products utilize proprietary technology, as well as technology licensed from SPF Innovations, and may be covered by one or more patents. See pall.com/patents.
Applications and Operational Benefits
The Cadence inline diafiltration module is designed for continuous processing, in-process buffer exchange or contaminant removal in various processes throughout a wide range of applications in the biopharmaceutical industry. These applications include buffer exchange for final drug substance, desalting or buffer exchange before or after column chromatography, and small molecule contaminant removal.
Enable continuous processing - Until now, there has been a gap in the technology offering for enabling diafiltration in a truly continuous, single-pass method. The Cadence ILDF device fills that gap and is facilitated through the use of staging, providing repetitive dilution / concentration cycles without a re-circulation loop and with significantly smaller system hold-up volume.
High removal factors - The Cadence ILDF technology allows for removal factors of ≥ 3-log. Dialing in the number of diavolumes is easily achieved by adjusting the flow rate on the buffer addition pump and performance is stable over extended operation times.
Optimize processing of highly shear-sensitive products - Processing results in only one pass through the pump and module, therefore reducing shear exposure. Further benefits are achieved by eliminating any mixing or foaming issues associated with the feed tank.
No holder required - Cadence ILDF modules come assembled, and the cassettes and manifolds are configured between two end plates with no extra holder needed. A pre-configured tubing manifold is also provided. Simply torque the device to the recommended setting and attach the tubing manifold to a feed pump and diafiltration buffer pump.
Product Platform Similar to other Cadence SPTFF devices, the Cadence inline diafiltration device utilizes standard Pall T-Series cassettes as the building blocks for the module. These modules are offered with either Delta regenerated cellulose or Omega polyethersulfone membranes providing the high flux, high selectivity and low protein binding characteristics that are associated with these membranes. They are available in a range of size formats to accommodate various processing volumes.
A standard PharmaPure♦ tubing manifold is provided with each device, and Sta-Pure♦ tubing manifolds can be ordered separately for extended operation applications (see ordering information).
The Cadence ILDF device requires two standard peristaltic pumps for operation. A 2-headed pump to control the feed and retentate, and a 6-headed pump to control the buffer injection. The feed and retentate lines on the supplied tubing set include PendoTECH pressure transducers and conductivity sensors. A PendoTECH PMAT pressure monitoring device is required to monitor the feed and retentate pressure, and a PendoTECH CMONT device is required to measure conductivity. A torque wrench is also required to torque the module to the recommended level.
The operating characteristics for any SPTFF process must be established by performing trials and analyzing the results. Pall’s team of technical specialists is available to assist in conducting trials to develop operating conditions necessary to achieve the desired process objectives.
Materials of Construction
|Cassettes||Delta regenerated cellulose or Omega polyethersulfone 30 kDa membranes with polypropylene screen, white polyurethane encapsulant with white pigment (O2), and medical grade silicone for the permeate seals|
|Gaskets||Medical grade, platinum-cured silicone|
|Manifold Plates||Ultra high molecular weight polyethylene|
|Connections||T01/T02 – female luer connection and cap: Polypropylene T12 – female MPC quick disconnect connector and plug: Polysulfone|
|Flowpaths||Polypropylene, polysulfone, and platinum-cured silicone|
|Pump Head Tubing||
|pH Range||2 – 13|
Typical Feed Flow Rates
|Module||Area (m2)||10 g/L Feed Flow Module Area (m2) Range (mL/min)||55 g/L Feed Flow Module Area (m2) Range (mL/min)|
|T01||0.11||0.5 – 10||0.5 – 4|
|T02||0.22||1.0 – 18||1.0 – 10|
|T12||1.20||5.0 – 90*||5.0 – 55|
Module Integrity Test
|Delta||4.1 barg (60 psig)|
|Omega||2.1 barg (30 psig)|
Forward Flow Rate
|Delta: < 538 sccm/m2 (< 50 sccm/ft2)
Omega: < 1600 sccm/m2 (<150 sccm="" ft2="" td="">
Shelf Life The shelf life of the Cadence ILDF modules, packaged in preservative, is expected to be 5 years from the date of manufacture when the modules are stored unopened in the original packaging at a temperature up to 25 °C and protected from direct light. The shelf life studies to confirm this are ongoing.
Biological Safety Materials of construction for the Cadence ILDF modules have been tested and meet the requirements for the Biological Reactivity Tests listed in the United States Pharmacopeia (USP) <88> for Class VI – 70 °C Plastics.
Figure 1Number of diafiltration volumes needed for Cadence inline diafiltration system compared with conventional TFF
Scaled operational performance across different sizes of the Cadence inline diafiltration modules. All modules tested with 40 g/L HIgG and 13 diafiltration volumes.
Figure 3Stable performance when operating over extended time. T02 modules tested with varying concentrations of IgG.
Stable aggregate profile over extended continuous processing performance when operating over extended time. T12 module tested with Pall in-house mAb.
Ability to adjust % removal with instantaneous adjustment of applied diafiltration volumes through pumping adjustment. Removal % adjustment at a constant feed flow rate using 60 g/L IgG.
Each module is supplied with the following comprehensive documentation to ensure the Cadence ILDF module is operated successfully.
- Certificate of quality
- Installation guide
- Material and safety data sheet (MSDS) for the module preservative solution
- Care and use manual*
- Validation guide*
- Validation service for your specific tests such as compatibility testing with your product fluid*
- Training and technical support to optimize your process using Cadence inline diafiltration modules*
Identify and order Cadence inline diafiltration modules using the table below.
Guide to Cadence Inline Diafiltration Module Part Numbers
|DF||Inline diafiltration device|
|DC/OS||Delta regenerated cellulose or Omega polyethersulfone membrane|
|030||Nominal molecular weight cut-off (MWCO)|
|06||Number of stages in series|
|12||Number of cassettes per module|
Cadence Inline Diafiltration Part Number and Membrane Area (m2)
|Part Number||Membrane||Cassette Format||Membrane Area (m2)||MWCO (kDa)|
Tubing Set Part NumbersNote: Every Cadence ILDF module includes a PharmaPure tubing set.
|Cadence ILDF T01/T02 PharmaPure||5390-0565M|
|Cadence ILDF T01/T02 Sta-Pure||5390-0565N|
|Cadence ILDF T12 PharmaPure||5390-0565P|
|Cadence ILDF T12 Sta-Pure||5390-0565Q|
Additional Recommended Equipment for Operation (not provided by Pall)*
|Masterflexu L/S pump||Cole-Parmer||EW-07522-20||2|
|Masterflex Easy Load II pump head||Cole-Parmer||EW-77201-60||2|
|Masterflex L/S cartridge pump head (6 channel, 6 roller)||Cole-Parmer||EW-07519-15||1|
|Masterflex♦ L/S pump head cartridges, large||Cole-Parmer||EW-07519-75||6|
|PendoTECH PMAT 4 pressure monitor||PendoTECH||PMAT4A||1|
|PendoTECH CMONT conductivity monitor||PendoTECH||CMONT||1|
|PendoTECH software licenses, 1 per PC||PendoTECH||PMATP-GUI||1|
|Masterflex mounting hardware (for 2 pumps heads)||Cole-Parmer||SC-77200-02||1|
|9/16 in. deep socket||McMaster-Carr||5544A45||1|