Key Process Parameters Study for the Fill Finish of Vaccines Containing Aluminum Hydroxide Adjuvant.

ABSTRACT

Vaccine manufacturing is one of the most challenging and complex processes in pharmaceutical industry, and the process control strategy is critical for the safety, effectiveness, and consistency of a vaccine. The efficacy of aluminum salt adjuvant on vaccines strongly depends on its physicochemical properties, such as size, structure, surface charge, etc. However, stresses during the vaccine manufacturing may affect the stability of adjuvant. In this study, the impacts of cold/thermal stress, autoclaving, pumping, mixing, and filling shear stress on the physicochemical properties of aluminum hydroxide (AH) adjuvant were evaluated as part of the manufacturing process development. The results showed that the autoclaving process would slightly influence the structure and properties of the investigated AH adjuvant, but thermal incubation at 2-8 °C, 25 °C and 40 °C for 4 weeks did not. However, -20 °C freezing AH adjuvant led to the adjuvant agglomeration and rapid sedimentation. For the high shear stress study with mixing at 500 rpm in a 1-L mixing bag and pumping at 220 rpm for up to 24 h, the average particle dimension of the bulk AH adjuvant decreased, along with decreasing protein adsorption ratio. The studies indicate that various stresses during manufacturing process could affect the structure and physicochemical properties of AH adjuvant, which calls for more attention on the control of adjuvant process parameters during manufacturing.