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

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


BioPharm International Supplements


Testing Needs and Documentation Expectations


Table 2. Sterile connector testing information provided by manufacturers†
The sterile connector manufacturers provide data on the extensive testing they perform as part of their validation package and lot release program. Although many of these tests are performed in different ways, they ultimately end up with similar outcomes. Much can be said about each of these individual tests, however, end users should review these data thoroughly to ensure that the sterile connector has been challenged using worst-case conditions for proper selection and to mitigate risk. A compilation of most of the common tests manufacturers perform or data they will provide is shown in Table 2. For some types of studies, attention must be paid to whether testing is done after gamma irradiation, autoclaving, aging, or no sterilization.

Burst testing confirms a maximum pressure that a connection can withstand. For the creeping and tensile testing, some of the suppliers claim these types of tests are only for plastics expected to undergo stretching, and others only perform these tests on the junction where the tubing meets the barbed or triclamped ending of the connector or where an adaptor is adhered to the connector end.

Regarding integrity testing, each manufacturer takes a slightly different approach. Testing includes dye leak, vacuum leak, air integrity, and helium leak testing. Some integrity tests are conducted according to standards (i.e., ASTM), whereas others use specialized manufacturing release integrity testers. Some of the manufacturers perform the test to confirm the integrity of each individual connector (i.e., male or female); others do this on the assembled connection. Some observations are performed by visible detection of leaks, yet others measure pressure change or helium detection. Technically, the most rigorous testing is the helium test, performed during both assembly and operation.

Particulates

The particulates test is done on a solution of water for injection after passing it through the connection. This can be done according to the pharmacopoeias. Alternatively, as in the case of the "particulate cleanliness test," for example, this testing also includes fibers and a broader range of particle sizes.

Bacterial Challenge

The bacterial challenge test typically is done by exposing the connector mating surfaces to a bacterial solution (by direct soiling or by aerosol) with a minimum colony forming unit (CFU) concentration, assembling the connection, passing sterile media through the connection, and collecting it. After incubation of the collected sample, absence of microbial growth confirms prevention of ingress of a contaminant. Proper controls must be demonstrated.

Extractables

Model solvent extractables are supplied by most of the connector manufacturers. Those devices composed primarily of polycarbonate are now also checked for bisphenol A (BPA) residuals because this substance, which can mimic estrogenic actions, is found in polycarbonates.1

LAL Endotoxin

The limulus amebocyte lysate (LAL) test has been completed by all but one of the suppliers, either as part of the validation or on every lot. The fifth manufacturer claims to be completing the test shortly.

Material Compliance

All of the manufacturers state that their connectors are composed of Class VI plastics and that they perform the USP biological reactivity testing in vivo. Some have completed the ISO in vitro or USP MEM cytotoxic elution testing as well.

For animal-free claims, all show compliance with regulatory bodies (i.e., EMEA, EC, or US CFR), especially because the plastics or plastics processing methods can contain trace levels of stearates, which typically are derived from bovine tallow. Tallow derivatives are not considered prohibited cattle materials according to the current revision of Title 21, of the US Code of Federal Regulations, part 189.5.2 Furthermore, an EMEA note for guidance (EMEA 410/01) has given specific consideration to tallow derivatives and it states that they are unlikely to be infectious because of the rigorous processing steps used.3


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