Biomedical Engineering Reference
In-Depth Information
present any hazard to the products. The parts of the production equipment
that come into contact with the product must not be reactive, additive or
absorptive to such an extent that it will affect the quality of the product and
thus present any hazard.”
The European Medicines Evaluation Agency (EMEA) published a guide-
line on plastic immediate packaging materials in December 2005 that also
addresses container-closure systems and has been used to provide direc-
tion for single-use process-contact materials. Data to be included relating to
extractables and leachables come from extraction studies (“worst-case leach-
ables”), interaction studies, migration studies (similar to leachable informa-
tion for those components), identify what additional information or testing is
required, and then set and execute a plan to fill in the gaps.
Risk Assessment
Risk assessment is based on the following considerations:
•
Compatibility of materials:
Most biological drugs formulations are
aqueous based, and therefore compatible with the materials used
in most disposable processing components. Still, a check to make
sure that the process stream and/or formulation do not violate any
of the manufacturer's recommendations for chemical compatibility,
pH, and operating pressure/temperature is warranted before pro-
ceeding. A full analysis of data generated by the vendor should be
completed upfront as a preparatory step.
•
Proximity of a component to the final product:
Product contact imme-
diately before the final fill increases the risk of leachables in a final
product. For example, tubing or connectors used to transfer start-
ing buffers probably present a lower risk because of their upstream
location. Processing steps such as diafiltration or lyophilization that
could remove leachables from a process should also be considered
because they may reduce associated risk. However, it cannot be
assumed that a step that can potentially remove some leachables
will remove all leachables. In such cases, supporting data should
be obtained.
•
Product composition:
In general, a product stream or formulation that
has higher levels of organics, particularly high or low pH, or solubi-
lizing agents such as surfactants (detergents), will increase the regu-
latory and safety concern for potential leachables. Neutral buffers
lower concern about potential leachables.
