Single Use, Ease of Use
In the decade since single-use components entered mainstream bioprocessing, the marketplace has been turning from individual components toward subassemblies, systems, entire processes, and even whole facilities. “It’s reached the point where manufacturing plants have become single-use entities,” Moussourakis says.
Although single-use has not quite yet matured to the point where customers can dial in and have any type of system gamma sterilized, dropped off, and ready to use, filters (and other components such as biocontainers and sterile connection/disconnection devices) are mostly plug and play.
Moussourakis relates comments he heard at a conference: “As one industry leader said, we want to be able to run a bioprocess in a conference room. That means all utilities—air, cooling, and heating—are delivered to self-contained, modular processes and run in unclassified clean space.”
With titers and cell densities rising, concerns over costs and quality are increasing, and risk mitigation has become the prevailing mindset. Single-use processing is but one component that facilitates risk-based manufacturing.
“Manufacturers are responding with higher performance and ease of use,” observes Gabriel Tkacik, director of filtration R&D at EMD Millipore. “Opportunities exist to further optimize and integrate filters with single-use systems to enable plug-and-play operation. Working closely with end users, filter manufacturers are improving the efficiency of biomanufacturing operations by addressing ease-of-use needs for single-use filtration systems.”
Since filters come into intimate contact with process fluids, materials of construction are critical to how filters fit into the “disposable” scheme of things. Consequently, one might think that by now, a full decade into single-use biomanufacturing, the issue of leachables/extractables would be settled. It isn’t, Tkacik explains: “Increased regulatory scrutiny and a broader desire for risk reduction are causing users to demand more information on filtration products.
“Biomanufacturers want to understand how filter materials might interact with process components and affect drug substance quality and stability. In addition, many users want to understand the manufacturing process and supply chain that supports their filtration products,” adds Tkacik.
Vikas Gupta, business leader for bioprocess filtration at GE Healthcare, notes significant emerging trends in bioprocess filtration: increasing filter integration with single-use systems, focus on reducing holdup volume, improved process monitoring capabilities in single-use filtration assemblies, and the resurgence of hollow fiber membranes.
The integration idea is related to ease of use. “The industry first transitioned from cartridges to capsules. Now we’re connecting capsules to single-use sterile connectors at the time of filter assembly, which offers a sterile, pre-rinsed, pre-washed sub-assembly right out of the box,” Gupta says. “This design reduces the number of connections, thereby reducing the risk of failure, and makes the filtration assembly optimally suited for use in a gray space environment.” GE’s ReadyToProcess filtration devices are one such offering in the market.
Due to the high value of process fluids, filter holdup volume has always been an issue in biopharmaceutical manufacturing because holdup equals lower product recovery. Holdup is becoming more serious now as processing volumes decrease and titers rise. Today, manufacturers employ various techniques to reduce holdup, but these add extra steps to the process. “Instead, the industry is trying to address the hold-up volume challenge through redesign of the filters themselves,” Gupta says.
Industry is also focusing on adding process monitoring capabilities to single-use filtration based unit operations, including buffer and media filtration, and cell harvest. According to Gupta, “filters used in single-use systems may now incorporate disposable sensors and meters for flow, pressure, temperature, and conductivity, thus achieving two goals with one piece of equipment in a predesigned flow path.”
Lastly, Gupta mentions the renaissance in hollow fiber filtration usage in cell harvest, especially in perfusion applications. “Conventional centrifuges do not lend themselves to continuous processing, whereas hollow fiber filtration integrated with a perfusion bioreactor can be fully integrated. The harvest step thereby becomes continuous by design.”