Biomedical Engineering Reference
In-Depth Information
for injectable drug packaging, particularly for highly active peptides and pro-
teins. Therefore, packaging should not only protect the product from leakage,
or contamination from foreign particles, at the same time it must also be fully
compatible with the product [26].
12.3.7.2 Quality Risk Management for Primary Packaging Process The major
risks associated with primary packaging process are discussed in the following
section.
Excipient Interactions Excipients aid in protecting the drug substance, sup-
porting and enhancing its stability, improving bioavailability, and in general
contributing to the overall safety and effectiveness of the drug substance. How-
ever, there is a risk that excipients may impact product quality by interacting
negatively with the primary packaging. For example, polysorbate 80 (PS80) is a
surfactant that is typically used to prevent protein aggregation in drug substance,
but PS80 can adsorb to glass surfaces and its levels can decline significantly dur-
ing storage, thus reducing its ability to prevent protein aggregation. Therefore,
it is important to evaluate the risk of potential excipient interactions with the
primary container closure during development studies.
Environmental and Chemical Hazards Biopharmaceuticals are proteins and pep-
tides molecules with unique chemical, physical, and mechanical properties. Pro-
teins are sensitive to heat, light, and chemical contaminants. As proteins and
peptides have a tendency to adsorb onto the surface of packaging containers
and closures, there is a risk that minute concentrations of metals, plasticizers,
and other materials from packaging may deactivate or denature therapeutic pro-
teins. This can essentially remove all active materials from the drug formulation.
For example, storing drug substances that contain sodium chloride in their for-
mulation in stainless steel containers is a risk because metal oxidation can occur.
In situations where the drug desorbs back into the solution, such interactions
could cause the drug to lose potency.
Many biotechnology products are also sensitive to silicone oil, a material
commonly used to lubricate elastomeric stoppers during fill/finish to facilitate
insertion of the stopper into the vial. However, silicone oil poses a risk to product
because it has been associated with protein inactivation through nucleation of
proteins around oil droplets. Recently, fluoroelastomer coatings on stoppers have
mitigated this risk and helped provide chemical inertness, barrier protection, and
safety for the product [27]. Therefore, it is important to perform risk analysis
studies to assess the interactions of environment and chemical hazards with the
packaging and to minimize product risk.
Packaging Operations Another major risk to the product is inappropriate pack-
aging/handling conditions. For example, most lyophilization cakes are sensitive
to moisture, and an inadequate seal on the vial could cause water and other con-
taminants to enter the package and deactivate the drug. Therefore, vial-capping
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