Single-Use Transfer Lines: Overview
Biopharmaceutical manufacturers are constantly implementing new ways to leverage existing plant infrastructure to enhance process reliability and flexibility. One solution that continues to gain momentum is single-use systems—particularly single-use transfer lines—which can deliver significant value through added flexibility, improved asset or equipment utilization and lower costs.
Initially, single-use systems consisted of tubing, bags, filters and connectors. Bioprocessing facilities used these systems for process storage applications and sterile cell culture media. Single-use bioreactors then entered the market in research and development labs and rapidly moved into pilot plants and larger scale production facilities as integral systems for production and seed train scale-up. Now, single-use transfer lines are used throughout the bioprocess to reduce operational costs. Unlike hard piping, the flexible tubing in single-use transfer lines does not require expensive and time-consuming cleaning and validation.
Manufacturers can more efficiently manage business cycles by quickly changing process steps or converting to a new product—a key advantage for multiple product facilities in which process requirements change with the drug being produced.
Innovative manufacturers now incorporate single-use transfer lines in the following:
• Seed Trains
• Suite-to-Suite Transfer
• Final Fill Applications
Single-Use Transfer Lines: Seed Train
You can use single-use transfer lines in conjunction with your existing processing equipment to reduce validation and maintenance costs with stainless steel piping and valves. For example, a 10,000 L production suite with stainless steel bioreactors can integrate single-use technology for cell culture media storage and key transfer lines.
• Single-use media storage systems arrive at the bioprocess facility sterilized by gamma irradiation and often fitted with integrated filters, sampling systems and connectors
• A single-use SIP connector allows operators to make sterile connections between these pre-sterilized single-use systems and stainless steel bioreactors for aseptic transfer of media
Similarly, operators can use single-use transfer lines to move inoculum between bioreactors, using either a peristaltic pump or headspace pressure.
• Such transfer lines can reduce the number of reusable valves required for transfer and can eliminate problem areas for CIP and SIP validation
• Terminating each pre-sterilized transfer line with a single-use SIP connector provides sterility assurance equal to that of traditional fixed piping at lower capital costs
Single-use systems are connected to a cell culture media storage bag—either by aseptic welding or with a CPC AseptiQuik® Connector—using flexible tubing. Likewise, flexible tubing with AseptiQuik® connections is used for transfer lines between each reactor in the process. For production volumes over 1,000 L, a single-use bioreactor must ultimately seed one or more stainless steel bioreactors. CPC Steam-Thru® Connections incorporated into the single-use bioreactor design can link the single-use and stainless steel section of a seed train.
For added safety, you can use an HFC39 quick disconnect coupling that has been validated as an aseptic disconnect to remove single-use bags and tubing after the media transfer is complete.
Single-Use Transfer Lines: Suite-to-Suite Transfer
Traditional bioprocessing facilities transfer medium from the production suite to a preparation suite by using stainless steel manifolds with piping or reusable hoses as transfer lines. 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. 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.
Process engineers now incorporate single-use transfer lines between the bioreactor in the process suite and the transfer vessel. Using pre-sterilized connectors and tubing, the medium can be moved from the production suite to the preparation suite without the need to sterilize stainless steel piping or equipment. This enhanced mobility eliminates many of the restrictions that hard-plumbed piping can place on the manufacturing facility and allows the manufacturer greater flexibility when determining which process to run in each production suite.
Especially in multiproduct facilities, the risk of cross contamination in the suite-to-suite transfer process is high and can potentially lead to product loss or reduced production yields. Pre-sterilized, single-use assemblies reduce these risks and improve the speed and safety of drug development and delivery.
Single-Use Transfer Lines: Final Fill Operations
Traditionally, final fill operations included stainless steel equipment connected via reusable valves, rigid tubing and steel pipes. Today, many process engineers are designing this operation with single-use transfer lines instead of stainless steel equipment to reduce sterilization time and cost.
Final fill tanks are designed to transfer formulated product from formulation suites to storage areas and ultimately to filling suites. To allow sterile connection to and from these vessels, designers traditionally added three-way valve assemblies to fill and drain ports. Replacing these heavy assemblies with single-use transfer lines and connectors eliminates cleaning validation and maintenance, while reducing mobile vessel weight by tens of kilograms.