Single-Use Transfer Lines in Biopharmaceutical Applications
By John Boehm, Bioprocess Business Unit Manager
& Brent Bushnell, Bioprocess Sales Manager
Colder Products Company
Biopharmaceutical manufacturers face increased pressure to commercialize new drugs faster and at a lower cost. As a result, production demand is outpacing available manufacturing capacity. To meet existing and future demand and maintain a competitive advantage, many manufacturers are striving to develop increased efficiencies within their manufacturing processes. This is where single-use systems - particularly single-use transfer lines - can deliver significant value, including added flexibility, improved production yields and increased cost savings.
Single-use systems, consisting of bags, tubing, connectors and filters, first gained acceptance in bioprocessing facilities for sterile cell culture media and process buffer storage applications. Following this, single-use bioreactors were developed and have quickly moved from research and development labs into pilot plants and production facilities as integral systems for production and seed-train scale-up. More recently, many downstream process engineers have overcome their initial reluctance to incorporate single-use systems and have added single-use as integral components of downstream purification and formulation steps.
The trend today is toward transfer lines or tube sets that use single-use connectors and filters to achieve sterile media transfer between process equipment or between production suites. A key benefit of single-use transfer lines is their ability to help boost productivity and accelerate time to market by reducing the downtime associated with cleaning and validation. This, in turn, helps reduce operational expenses by minimizing labor, chemical, water and energy demands. Additional cost savings stem from reduced validation efforts, greater speed to market, and more flexible manufacturing facilities.
Fixed tubing and re-usable valves require cleaning and cleaning process validation between production batches to maintain desired sterility. Single-use components on the other hand, are provided pre-cleaned and pre-sterilized, effectively "outsourcing" the cleaning and sterilization activities required in a traditional operation. This not only reduces labor time and expense, it also improves the speed and safety of drug development and delivery. Pre-sterilized, single-use assemblies reduce cross-contamination risks that may lead to product loss or reduced production yields.
This benefit is further magnified for companies that conduct multi-product manufacturing within single facilities. Unlike hard piping, the flexible tubing incorporated in single-use transfer lines allows manufacturers to quickly change process steps or convert over to a new product. This is a key advantage for multiple-product facilities in which process requirements change depending on the drug being produced.
One application for single-use transfer lines is in the aseptic transfer of inoculum through a seed train of stainless steel bioreactors (see Diagram 1). A traditional facility will feature one or more series of bioreactors that increase sequentially in capacity and are connected by CIP/SIP piping. Replacing the fixed piping with single-use transfer lines eliminates the need for CIP validation and reduces maintenance and capital expense by eliminating expensive valve and sanitary piping assemblies. Transfer lines can also increase process flexibility. Using an SIP connector like the Steam-Thru® Connection allows operators to independently steam-on both ends of the transfer lines when sterilizing each bioreactor. Transitioning the SIP valve into the flow/open position allows aseptic transfer of inoculum using either head-space pressure from the seed bioreactor or a peristaltic pump. Additionally, since the connections between seed bioreactors can be easily changed, maintenance of one bioreactor in a train series would not prevent use of the other bioreactors.
Lasting ImplicationsAs more manufacturers take advantage of single-use systems, their integration with traditional stainless equipment will continue to increase. All biopharmaceutical manufacturers can benefit, but biotech start-ups gain both the operational advantages of incorporating single-use systems while also saving time and expense in the design, build and validation of new facilities. Existing production facilities are being retrofitted with single-use transfer lines to increase capacity and improve production yields with minimal expenses.
Bottom line: the benefits of single-use transfer lines aren't limited to upstream or downstream processes, large or small operations, or new or retrofit facilities. Whether it's connecting within a process or across different processes, this is a technology with bottom line advantages throughout the manufacturing operation.
About the authors: John Boehm is the bioprocess business unit manager at Colder Products Company Brent Bushnell is the bioprocess sales manager at Colder Products Company (www.colder.com), headquartered in St. Paul, MN.