Disposables for upstream and downstream processing were among the lead topics at IBC’s recent “BioProcess International” meeting held in Raleigh, NC. In addition to their convenience and cost-reduction contributions, their use has been shown to result in reduced exploitation of water and electrical requirements. A number of presentations at the meeting dealt with new filtration technologies, many of which take advantage of disposable modules.
Single-pass tangential flow filtration “is a patented technology that enables high concentration factors in a single pass and delivers the performance of tangential flow filtration with the simplicity of direct flow filtration,” stated Steven Pearl, vp for biopharmaceutical R&D at Pall Life Sciences. “The technology results in more compact systems due to its reduced flow-rate requirements and simple control scheme.”
According to Pearl, the configuration of Pall’s single-pass system is much more straightforward than conventional tangential flow filtration, substituting a flow ratio meter controller for a recirculation loop, thus allowing a lower working volume without risk of foaming. The fluids are passed directly through the system, so there is no need for a reservoir to accumulate batches.
Pearl described a number of advantages of the technology, including preassembled, easy-to-install modules, whose optimized flow path permits smaller pumps and tubing. The short resident time means shear forces and viscosity of exposure of the solution will be less. Moreover, process control is reportedly tighter, there is a higher total recovery while at the same time flush volumes are reduced. In addition, single-pass cleaning is purported to save materials and labor.
"The fact that we can work with reduced volumes means that we avoid having to install larger tanks, slow down the process or split the batches," Pearl observed. "We can employ a simple in-line regulator module with the ability to concentrate our volumes by as much as 10 fold. We can also lower salt concentrations during processing to improve the performance of the ion exchange chromatography steps without dilution."
The gleam of stainless steel is much less in evidence in today’s bioprocessing facilities as disposable aseptic filtration units replace the traditional reusable equipment, according to Michael Labreck, sales manager at Novasep. The company has developed disposable units for tangential flow filtration that are pre-sanitized and prepacked in 0.2M NaOH, ready to use. The modified polysulfone membranes are available in a wide range of molecular weight sizes and are designed for low protein binding.
“The performance of our Sius Single Use TFF cassettes will meet or exceed the performance of traditional, reusable TFF cassettes,” Labreck said. “We have engineered features for additional labor savings and better process economics.”
Michael Xenelis, senior development associate at EMD Serono, reported on his company’s use of Sius TFF disposable units. EMD has replaced the step requiring an anion-exchange column with a membrane, and traditional tangential flow filtration cassettes have been replaced with disposable Sius membranes at the initiation and conclusion of the run.
Replacing the anion-exchange column with a Q membrane generated a myriad of benefits, according to Xenelis, including reduction in buffer usage, set-up time, amount of documentation, and maintenance requirements. The membrane comes ready to use from the box, avoiding laborious column packing, and water saving are significant—60 L of innocuous buffer per run in the disposable situation, as opposed to 350 L in the case of the reusable units.
“The final UF/DF tangential filtration step had previously been the longest and most problematic,” explained Xenelis. “This was a major source of frustration for operators, since flux recovery was poor, buffer demand high, and presumably reusable membranes had to be discarded after a single-use cycle.”
Use of Novasep Sius membranes for tangential flow filtration, Xenelis explained, allowed the elimination of many steps, much attendant time, and resulted in consumables savings. Total process time was cut from 10.4 hours to 5.1 hours, including installation. Additionally, reductions in the protein A column size allowed a savings of $37,000 in protein A resin and buffer costs.
“Through the implementation of the Sius TFF disposable cassettes we were able to reduce costs of buffer, bags, labor, and materials by half or more. For these reasons they are now our standard choice for all new projects.”