Vial Fogging in Lyophilized Biologics: From Haze to Clarity: Poster Presented at PDA Week 2026.

Vial fogging is a common but poorly understood phenomenon in lyophilized biologics. It presents as a hazy dried powder on the inner surface of the vial. While it is a cosmetic defect, severe fogging that reaches the vial neck or shoulder area could cause container closure integrity issues and rejection of batches. Besides, the phenomenon can be exacerbated at full-scale manufacturing. Fogging is influenced by several factors such as formulation characteristics, vial surface properties, dehydrogenation temperatures, and lyophilization process parameters. We investigated fogging using a placebo formulation and proprietary formulation and evaluated fill volumes, surfactants, specifically polysorbate 80, dehydrogenation temperatures, and different vial types. The case studies identified critical factors that affected the severity of fogging. We also present mitigation strategies to eliminate it.