Testing Needs and Documentation Expectations
Table 2. Sterile connector testing information provided by manufacturers†
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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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