Effectively Securing Cell and Gene Therapies with Closed Systems

With their innovative new treatments, cell and gene therapies (CGT) are growing rapidly. But their traditional production processes don’t allow the supply of these therapies to keep up with demand.

Historically, these therapies are produced for small patient populations in clinical trials using laboratory scale equipment and utilizing manual, open processes completed under laminar hoods. But manufacturers looking for more efficiency and flexibility are turning to new solutions. One key area of interest is the implementation of a closed system design utilizing single-use technology (SUT).

Closed systems in CGT provide the protection of a cleanroom against outside contaminants without the costs associated with maintaining it. CGT manufacturing that uses open processes at lab scale to create smaller batch sizes is still slow to adopt closed systems.

When transitioning from connecting processes in biosafety cabinets to closed system connectivity, the final process must be able to scale up from lab equipment to larger scale bioreactors with ease. This is often done through the use of tube welding/sealing or aseptic connectors.

While tube welding is considered a sterile connection, it can pose several problems. While the tubing does not contain product at the time of welding, once the tubes are welded and product begins to flow, any foreign particulates left behind could get into the product. If the weld is done improperly, there is also the risk that the flow path in the tubing may be partially blocked during the sealing process (occlusion). This could place extrinsic particulates in the flow path. Heat and pressure during welding can also create extractables from the tube, depending on the material it’s made from, which could affect healthy cell populations. Tube welding is also done in GMP processes, so there is no pre-validating done to ensure contamination did not occur.

Conversely, single use connectors offer an easy method for maintaining flow path sterility and integrity while enabling the protection needed to avoid costly failures from contamination.

CPC’s AseptiQuik® family of single-use connectors offer several benefits. They utilize a simple three-step connection process that consists of “flip-click-pull.” This reliable process reduces the risk of operator error and easily creates a sterile connection. They can also be frozen down to -80o Celsius for therapies with cold temperature requirements.

CPC AseptiQuik connectors are genderless, which means they connect regardless if the equipment they are attaching to has a “male” or “female” connection. This allows manufacturers the freedom to explore various equipment providers for the most economical solutions.

What’s more, extensive extractables studies have been completed on SUT, so CGT manufacturers know their equipment won’t impact the safety and quality of their product. CPC has also adopted and executed the BioPhorum Operations Group protocol on its single use connectors because it recognizes the critical need for extractables testing.

With increasing demands for efficiency and economy being placed on the CGT market, partnering with suppliers who can provide guidance in areas such as best practices in closed system design may give manufacturers the edge they need to be successful.