Modern bioprocessing facilities scale up inoculum from a few million cells in several milliliters of culture to production volumes of up to 25,000 L or more. This process requires aseptic transfer at each point along the seed train. Traditional bioprocessing facilities accomplish scale-up using a dedicated series of stainless steel bioreactors linked together with valves and rigid tubing.
To prevent contamination between production runs, a clean-in-place (CIP) system is designed into each bioreactor, vessel, and piping line to remove any residual materials. These CIP and steam-in-place (SIP) systems require extensive validation testing, and the valves and piping contained in these systems can create additional validation challenges.
Advances in single-use technology allow bioprocess engineers to replace most storage vessels and fixed piping networks with single-use storage systems and tubing assemblies (Figure 1). Single-use eliminates the need for CIP validation for many components and reduces maintenance and capital expense by eliminating expensive vessels, valves, and sanitary piping assemblies.
Single-use media storage systems are routinely manufactured for volumes from 20 to 2,500 L. Media storage systems arrive at the bioprocess facility sterilized by gamma irradiation and often are fitted with integrated filters, sampling systems, and connectors. Using an SIP connector like Colder Products’ Steam-Thru® Connection allows operators to make sterile connections between these presterilized single-use systems and stainless steel bioreactors for aseptic transfer of media.
Similarly, single-use tubing assemblies may be used to transfer inoculum between bioreactors using either a peristaltic pump or head-space pressure. Such transfer lines can reduce the number of reusable valves required for transfer and eliminate problem areas for CIP and SIP validation. Terminating each presterilized transfer line with a single-use SIP connector provides sterility assurance equal to that of traditional fixed piping, at lower capital costs.