The Next Step in Implementing Disposables July 2008

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.

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.

Real-World Results

One application for single-use transfer lines is in the aseptic transfer of inoculum through a seed train of stainless steel bioreactors. 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 headspace pressure from the seed bioreactor or a peristaltic pump. Additionally, because 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.

The flexible benefits of single-use transfer lines also apply to suite-to-suite transfers. In most bioprocessing facilities manufacturers have separate suites dedicated for distinct processes, e.g., fermentation, harvest clarification, chromatography, or formulation. Traditionally the processes have been linked together via stainless steel pipes that run through a wall or ceiling to connect one suite to another. Now manufacturers can simply run a single-use transfer line through a transport door to quickly and easily link one suite to another. In facilities originally designed for a single process but retrofitted for another, single-use transfer lines offer bioprocess engineers the flexibility to reroute process flow and bypass steps unnecessary in the new process.

Single-use transfer lines also allow bioprocessors to maintain process safety by creating closed loops, even with discontinuous process steps. For instance, formulation facilities often blend several sterile solutions to create the final drug product. Each solution may be stored for days or months in mobile stainless steel vessels that can be rolled into the formulation suite for mixing in a fixed blending tank. Single-use transfer lines may be designed to maintain a closed-loop, aseptic system when connecting mobile tanks to a blending tank. There are many options for connecting formulation transfer lines including configurations using a combination of SIP connectors, aseptic connections and weldable tubing.

Lasting Implications

As more manufacturers take advantage of single-use systems, their integration with traditional stainless equipment will continue to increase. The benefits of single-use transfer lines are not 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.