The risk of cross-contamination in the suite-to-suite transfer process is high, especially in multiproduct facilities. Presterilized,
single-use assemblies reduce these risks and improve the speed and safety of drug development and delivery. Such assemblies
are used in processes requiring a flow rate of less than 30 liters per minute, but more recently, suppliers have increased
the diameter of single-use tubing and SIP connectors to enable bioprocessing facilities to incorporate single-use transfer
lines into larger and larger production processes.
Final Fill Operation
The final step in the production process is transferring the product from the transfer vessel or bags into smaller vials,
bottles, or containers for distribution. In the past, the final fill operation consisted of stainless steel equipment connected
by reusable valves, rigid tubing, and steel pipes. This equipment also requires validation and must be subjected to a CIP
cycle after each filling cycle is completed. Today, many process engineers are designing this operation with single-use transfer
lines to reduce sterilization time and cost.
One example of integrating single-use systems in a final fill operation is to simplify mobile stainless steel transfer tanks.
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 add three-way valve assemblies to fill and drain
ports to facilitate SIP operations. The design of these three-way valves makes it difficult to validate cleaning procedures.
In addition, these valves require regular maintenance and may add significant weight to mobile vessels, especially in tanks
with multiple inlet and outlet ports. Replacing these three-way valve assemblies with single-use transfer lines eliminates
cleaning validation and maintenance steps while reducing mobile vessel weight by tens of kilograms.
Single-use transfer lines can be attached before vessel SIP sterilization with SIP connectors (used as either steam access
or condensate drainage sites), or steamed separately, just before fluid transfer. For vessel outlet, combining a number of
single-use components into the transfer line can create a very robust system to ensure product safety. For example, outlet
transfer lines could incorporate a single-use SIP connector to attach to the sterile holding tank. Then, a through-the-wall
fluid transfer system is used to bring a portion of the transfer line into an isolator where filling occurs. Next, a quick-connect
fitting or aseptic connector is used to attach the transfer line to the filling machine.
Figure 4.
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Figure 4 depicts a mobile transfer vessel with multiple single-use inlet lines and a complete outlet line system.
Conclusion
As more manufacturers take advantage of the benefits of single-use systems, their integration with traditional stainless equipment
will continue to grow. All biopharmaceutical manufacturers are able to benefit greatly from single-use systems, but biotech
start-ups can gain additional operational advantages by saving time and expense in the design, building, and validation of
new facilities. Manufacturers also benefit by retrofitting existing facilities with single-use transfer lines to increase
scheduling flexibility, production capacity, and improve production yields with minimal expenses.
Single-use transfer lines are not limited to upstream or downstream processes and the benefits can be seen in all operations
(large or small), or new and existing facilities. Whether it's connecting within a process or across different processes,
this is a technology with bottom line advantages throughout the manufacturing operation.
John Boehm is the bioprocess business unit manager at Colder Products Company, St. Paul, MN, 651.645.0091 john.boehm@colder.com
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