A Review of Sterile Connectors - Many factors must be considered when choosing a sterile connector for a given process. - BioPharm International


A Review of Sterile Connectors
Many factors must be considered when choosing a sterile connector for a given process.

BioPharm International Supplements

Narrowing Connector Selection

First, one needs to be familiar with the application to identify where and how to introduce these sterile devices. Is a wet or dry connection required? What size of tubing is needed? Is product visibility through the connectors important? What are the operation and storage requirements? What is the maximum operating pressure? These easily rule out some of the options.

More specifically, ease of use weighs heavily over other aspects, because when we compared them, we found that a few of the connectors required brute strength to operate. Fortunately, some of these connection manufacturers are aware of this problem and are currently addressing it. The number of connection steps (including cap removal) and timing of each connection should be optimal for one's process and operators. For two of the available devices, the addition of an assembly aid to facilitate alignment or a clamp to secure the connection adds to procedural complexity.

Table 1. Initial product aspects for comparison of sterile connectors†
Table 1 summarizes these and other factors to consider in the initial evaluation process; however, the names of each brand have been coded to avoid bias. Because some of the findings are qualitative, a thorough assessment should be done by each user.

Figure 2. Spatial considerations. Cleanroom or isolator wall pass-throughs or fittings may require a sterile connector assembly to be drawn through partially.
The geometry of the device is another criterion to consider. Some manifolds require several connectors in an assembly to attach a number of containers or lines. A longer connection adds length to the overall process; this can be problematic when the lines are longer than the working area or available space for equipment integration. Outer diameter and weight of these items also play a role. Product footprint and general bulkiness must be taken into account when transporting, assembling, and, if required, when passing devices through a wall or isolator fitting (Figure 2).

Fortunately, there are technologies that now exist to address the latter. Flow restrictions, based on the inner geometry of the connector and the connected tubing, can affect the processing system, especially with respect to fluid velocity, fluid type (i.e., suspension, culture), and viscosity. In some cases, it may be desirable to step up or down a connection size, and, fortunately, the manufacturers have ensured the connector ends can be mated for this very purpose (i.e., a " female can be connected to a " male). Other considerations in selecting a device are the stage of manufacturing and duration that the product will sit in the transfer lines, because those factors can affect the degree to which product contact materials affect product and vice versa. Manufacturers' claims of shelf-life should be reviewed carefully because it is not always clear whether the expiration date is based on real-time aging, accelerated aging, pre- or post-sterilization, or a combination of these. It also should be noted that some manufacturers have ongoing aging studies to extend their current shelf-life claim.

Assembly Considerations

A single-use assembly provider should be flexible when working on a client's design that includes sterile connectors. Tubing types, methods of securing tubing onto connectors (i.e., cable ties, barblocks), and willingness to use customer-specified components (i.e., those of their competitors) are aspects that should be considered when customers are selecting suppliers. Other factors to consider are sterilization options, gender-specific assemblies, and pricing.

Typically, two options are available for sterile connectors. The manufacturer may provide the connector on an assembly that has been presterilized by gamma irradiation. Alternately, connectors may be autoclaved along with assemblies made in-house. In addition, covering caps or packaging around the connectors may or may not be required for sterilization purposes. Finally, some of these devices cannot be autoclaved after irradiation. Suppliers must be able to demonstrate that all the materials of the connectors, both product contact and nonproduct contact, are compatible with sterilization.

All but one of the connection devices are gender-specific. When ordering a manifold, advanced planning of these assembly designs ensures that the correct gender-specific ends are present to connect with the mating end. This can be challenging when a manifold design is in early-stage manufacturing and changes may be made in the future. Adding extra connector ends to manifolds as a backup for sampling or transfer lines also can be a good precautionary step to take. However, this should not be necessary for finalized process designs. Genderless connectors consume less storage space in inventory because stocking does not require accounting for two different connector ends.

Price is an essential aspect of the evaluation, especially if the processes require a number of connectors or if there is a high turnover of batch manufacturing. In cases where, for example, thousands are used annually, an annual cost comparison with other alternatives may need to be done.

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