Training in the use of these consumables is highly recommended to ensure they provide an integral connection. Implementing
these products involves a number of steps and some require careful attention to avoid such mishaps as over- or under-actuation,
misalignment, displacement of o-rings, and interference with membranes (i.e., peeling them off inappropriately). Many of the
connectors have built-in safety features to avoid some of these potential troubles.
To ensure a good training program and good operation we recommend the following steps:
- Have vendor onsite demonstrations to show functionality and review the key features and operation.
- Train against well-written internal work instructions or operating procedures.
- Practice with complete assemblies and connections to other parts of the system.
- As required, include training on use of aids or clamps.
- Count clicks throughout the connection steps (if applicable).
- Review any visible differences after certain methods of sterilization (i.e., expected color changes).
If assembling the manifolds in house and autoclaving them, one must review with the manufacturer which securing aids are most
appropriate to affix to the connectors in addition to autoclave wrapping scenarios.
Vendor validation data are the most valuable references when it comes to having a complete testing and evaluation package.
For incorporation into GMP manufacturing, most end-users will do a process media simulation (also know as a broth validation),
whereby sterile broth is run through the processing lines including the sterile connectors.
Some end-users may do additional testing as part of their validation studies, dependent on specific product considerations.
This may include a confirmatory integrity evaluation using pressurized gas and monitoring to detect leaks, a leachables study
after a representative product solution is run and held through the devices, or a confirmatory bacterial challenge test. However,
it is hoped that, in most cases, vendor-provided data obtained from testing under controlled or worst-case conditions will
relieve the end-user from these additional burdens.
Finally, there are times when a user needs to ship a biopharmaceutical product from one location to another in a container
with a sterile connector end on it. A shipping qualification may be performed to verify that a sterile connection can still
be made after shipment because of packaging configuration, temperature, vibrations, handling, or bumping. There are many ways
to go about this, including testing for contamination of a sterile broth-filled system, leak testing, or using more sophisticated
packaging testing equipment to simulate or check for damages.
Performance testing will verify function after expected or exaggerated conditions. Some examples include:
- post-sterilization—post autoclaving or gamma irradiation
- repeatability—testing several connections in the same condition to determine a statistically relevant failure rate
- various temperatures—after or during low or high operating or after low or high storage temperatures
- worst-case solutions—after transferring and holding various worst-case solutions
- disinfection—after applying outer components with a cleanroom disinfectant
- worst-case flow rates—during use with process-specific pumping mechanisms
- worst-case pressure—during application of fatigue and pressure cycling or safety pressure testing.
Many of these conditions can be combined into one test but this should be verified with the manufacturer to confirm suitability
with their connectors and assemblies.