Investigation of Fogging Behavior in a Lyophilized Drug Product

Vial "fogging" is a common observation in lyophilized biological products and has been reported in the pharmaceutical industry. In addition to unappealing appearance, severe fogging that reaches the shoulder or neck of the vial can potentially compromise the container closure integrity of the vials. In this study, we performed experiments to identify parameters impacting the fogging phenomena in lyophilized drug product vials. Glass vial surface properties were found to have a significant impact on vial fogging. In line with prior published research, the study demonstrates that fogging can be mitigated by using glass vials with hydrophobic surface (such as siliconized vial or TopLyo® vial) and by extending the prefreeze 5°C hold during the lyophilization cycle. Moreover, this study shows that extending the annealing at -5°C or -10°C can also significantly reduce the fogging. Increased formulation viscosity and exclusion of a surfactant can mitigate the fogging behavior of the lyophilized product. The study shows that container closure integrity as determined by headspace analysis and vacuum decay is not compromised for the "fogging" drug product vials for this model monoclonal antibody container using a worst-case model of lyophilized "neck-wet" vials.