Final Fill Operation
The final production step is transferring the new medium from the transfer vessel or bags and into vials for distribution. Traditionally the final fill operation consisted of stainless steel equipment connected via reusable valves, rigid tubing, and steel pipes. Again, this equipment 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 tubing assemblies in place of stainless steel piping to reduce sterilization time and cost.
One example of integrating single-use systems in a final fill operation is for simplifying mobile stainless steel transfer tanks. These tanks are designed to transfer product from formulation suites to storage areas and ultimately to filling suites. To allow sterile connection to and from these vessels, designers traditionally 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. Replacing these heavy three-way valve assemblies with single-use tube sets and connectors eliminates cleaning, validation, and maintenance.
Single-use tubing assemblies can either be attached prior to equipment sterilization with single-use SIP connectors (used as either steam access or condensate drainage sites), or steamed separately, just prior to fluid transfer.
For vessel outlet, combining a number of single-use components into the transfer line can create a 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 the filling suite. Next, a sterile connector is used to attach the transfer line to a separate portion of the transfer line that has already been steamed onto the filling machine with a single-use SIP connector. Finally, disconnecting the transfer lines using a quick disconnect coupling that has been validated as an aseptic disconnect enables the processor to confidently make an aseptic disconnection from the storage vessel or bag.
Figure 3 depicts a mobile stainless bulk storage vessel with a single-use transfer line feeding the final fill equipment. The stainless vessel could also be replaced with a single-use bulk storage container.