Sterility Assurance: Overview
As biopharmaceutical manufacturers gain firsthand experience with the benefits of incorporating single-use systems into their facilities, they’re now expanding the use of these systems in both upstream and downstream applications. This is no surprise, as increased volume and diversity of pharmaceutical products is compelling manufacturers to design their facilities based on shorter production runs with multiple changeovers. Meeting these demands requires operational flexibility. Production facilities must be able to easily add new products, rapidly convert processes and quickly make operational adjustments as needed. This is where CPC’s single-use systems can deliver significant value: These systems offer many benefits, including rapid implementation and cost savings.
Innovative manufacturers now incorporate single-use transfer lines from CPC in the following:
• Adapting Facilities for New Products
• Creating a Completely Sterile TFF Loop
• Steam-Thru® Technologies
Sterility Assurance: Adapting Facilities for New Products
Although many biomanufacturing facilities were designed around Clean-in-Place (CIP) or Steam-in-Place (SIP) equipment and fixed stainless steel piping, adapting these facilities for new processes reveals the significant advantages of single-use systems.
One major manufacturer implemented a new process that required flushing of a critical filter element prior to filtering their final drug formulation. This single-use, SIP filter is encased in a stainless steel housing that was not piped for a filter-flush step. Their solution was to design a single-use bag system with a CPC Steam-Thru® II Connection inlet to capture the flush solution. This bag system is received pre-sterilized and routed through their cGMP raw material inspection and release process.
When preparing the filter for SIP sterilization, the bag is connected via the Steam-Thru® II to the filter housing’s bleed port. During SIP, steam passes through the filter housing, out the bleed port, into the Steam-Thru® II middle port and out the lower port to a steam trap. Once SIP is complete, the Steam-Thru® II valve is transitioned to the flow position creating a sterile flow path for collecting the flush solution. After the filter flush is complete, the Steam-Thru® II valve is transitioned back to the steam position, which isolates the bag system and flush solution.
Sterility assurance is the primary reason the manufacturer selected a single-use bag system with the Steam-Thru® II as an inlet:
“When filtering during drug formulation steps, maintaining sterility is an absolute priority. The combination of pre-sterile bags and the Steam-Thru® II provides the assurance we need without additional process equipment.”
Another factor considered was Steam-Thru® Technology’s track record:
“We’ve used Steam-Thru Connections for several points upstream in other processes over the past few years, so when we identified this new problem downstream, we knew that Steam-Thru would meet our requirements.”
Integrating single-use components with traditional stainless steel processing equipment can help manufacturers increase flexibility and adapt facilities for new processes, while maintaining process and product sterility.
Sterility Assurance: Creating a Completely Sterile TFF Loop
A major biopharmaceutical manufacturer selected CPC’s Steam-Thru® Connections as part of their downstream tangential flow filtration (TFF) system out of concern for maintaining process sterility. Their specific technology consists of two-layer microspheres composed of biopolymers about the size of red blood cells. This size creates a serious problem for downstream processing: unlike therapeutic proteins, once the biospheres are assembled, they cannot undergo any sterile filtration steps at 0.1 to 0.2 μm. This required the downstream engineers to design a robustly sterile process system.
One critical purification step was microfiltration TFF. To meet their sterile assurance requirements, the manufacturer developed a sterile TFF loop consisting of both reusable stainless steel and single-use components. “Using Steam-Thru, we can connect our single-use waste collection bag in advance and sterilize the connection point when we SIP our stainless steel retentive vessel. After actuating the Steam-Thru valve, we’ve created a completely sterile TFF loop with both reusable and single-use components.”
Ease-of-use and storage issues are other benefits of the system:
“Steam-Thru Connections are lightweight compared with steamable valve assemblies. Our 200 L single-use bag system with the Steam-Thru doesn’t require much storage space allowing us to keep 1000 L or more of waste collection capacity on a couple of shelves. Cleaning one vessel instead of two for our TFF is also a big plus.”
Integrating single-use systems into the microfiltration TFF process can help manufacturers streamline process steps and reduce cleaning and validation, while providing the assurance of a completely sterile TFF loop.