Filters have been a part of bioprocessing since the beginning. Yet “broad optimization potential” still exists for established processes and in filter selection for new processes, according to Holger Bromm, marketing director for filtration technologies at Sartorius Stedim Biotech.
“Our product development in the last few years has focused on specific applications such as media and buffer prep, and filtration of downstream intermediates, which are core applications within bioprocesses.” Even within these categories filterability can differ significantly, for example, supplemented versus chemically defined media, or mAb product pools just before and just after capture/elute.
For these distinct applications, Sartorius Stedim has introduced the Sartopore® 2 XL product line, which is based on Sartopore 2 products but carries prefilter membranes optimized for specific applications. Two such products have been developed for media and downstream applications and one each for sterilizing-grade filtration and mycoplasma. To further optimize performance and reduce filtration cost per liter the company increased the effective filtration area by 30%.
As bioprocess streams become more complex, prefiltration becomes increasingly necessary. “Contaminants need to be removed reliably to protect more expensive sterilizing-grade and mycoplasma-retentive filters,” says Bromm. He notes that, while polyether sulfone (PES) membranes are now well accepted due to their excellent flow and throughput characteristics, PES has not been widely employed for prefiltration. Sartorius Stedim has addressed this deficiency through its Sartoguard PES membranes, which, according to Bromm, “transfer the benefits of PES membranes to prefiltration and help reduce costs further.”
Replacing Unit Operations
Rising volumetric productivity is causing bioprocessors to downsize from very large stainless steel reactors to vessels in the 1 kL to 2 kL range. As a result, some firms are switching from centrifugation to disposable depth filtration at the harvest step, according to Jon Petrone, vp of technical services at Pall. Centrifugation is a capital- and labor-intensive operation that serves very large batches well, where the cost of using multiple depth filters would be high. But at 1–2 kL a batch may be harvested with one disposable depth filter, without the need to acquire, inventory, and store capital equipment.
Filtration also plays a role in concentrating proteins post-harvest, and later on in the formulation of the drug product. “We’ve seen some processes lower volumes by a factor of 10 or 20 at this stage, further reducing downstream volumetric demands,” Petrone notes.
Viscosity becomes a serious product recovery issue at these concentrations, which can reach 80 g/L or more. Significant product can remain behind when it drains out after conventional tangential flow filtration (TFF). Flushing out product requires adding buffer, which dilutes the process stream. Pall’s solution is its Cascade single-pass TFF, which provides direct flow-through concentrations with no recirculation of product required. The company claims protein recoveries of greater than 98% at concentration factors greater than 20 times.
Single-pass TFF works similarly well just prior to final formulation, where drug substance concentrations may reach a syrupy 250 g/L. “With single-pass TFF the only dilution occurs from chasing out the holdup volume,” Petrone says. “It is no longer necessary to sacrifice product recovery for high concentrations.”