A common primary container for storage of parenteral drug products is the borosilicate glass vial. Disadvantages of borosilicate glass vials include the presence of glass particles and metal ion contaminants in formulations which may affect drug product stability, and a less controlled manufacturing process leading to high dimensional variability. In this study, we compared the stability of therapeutic protein formulations in new primary containers composed of cyclic olefin polymer (COP) with novel silica-based coatings to conventional borosilicate glass. Vials containing liquid protein formulations were subjected to stresses that may be encountered during shipping and handling including mechanical-shock and freeze-thaw cycles. Glass, uncoated COP, and silica-coated COP vials containing an IVIg formulation were dropped using a Lansmont drop-shock tester and particle concentrations in formulations were measured using micro-flow digital imaging. Particle concentrations in formulations increased after mechanical-shock stress in all vial types and formulations in silica-coated COP vials had generally lower particle concentrations and a smaller deviation of particle concentrations compared to those in glass vials. Addition of surfactant to formulations prevented a significant increase in particle concentrations in dropped vials. We also tested the performance of silica-coated COP vials for lyophilized drug products by first evaluating the frequency of vial breakage during lyophilization of a mannitol formulation. Two thirds of the glass vials shattered or cracked during lyophilization of the mannitol formulation, whereas all silica-coated COP vials remained intact. Particle concentrations in vials that remained intact after lyophilization were lower in the formulations in silica-coated COP vials than those in glass vials. Additionally, we determined vial heat transfer coefficients and designed optimal lyophilization cycles for pharmaceutically-relevant formulations in the silica-coated COP vials.

Container-formulation interactions: A comparison of borosilicate glass vials and cyclic olefin polymer vials with novel silica-coated surfaces

253rd National Meeting (2017)

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