Desarrollo de la formulación, escalado y estabilidad de la vacuna antialérgica de Dermatophagoides siboney adyuvada con gel de hidróxido de aluminio

Adsorption of allergenic proteins onto aluminum hydroxide gel (AHG) is important for the safety and efficacy of vaccines used for allergen-specific immunotherapy. The adsorption of Dermatophagoides siboney dust mite allergen to AHG can be hampered by phosphate buffer (PBS). The aim of this work was to assess changes of product composition, in terms of reducing the content of PBS and AHG, as well as, removal of thiomersal, both at laboratory and GMP pilot scale. A factorial design was used to evaluate the influence onto antigen adsorption of two independent variables: PBS and AHG content. Three batches of three formulation variants with gradual reduction of AHG (0,5 - 2 mg/mL) and PBS (1 - 10 mmol/L) content, together with a control variant were prepared at pilot scale. The adsorption of Der s 1 allergen and total allergenic activity were measured by ELISA and a real-time stability study was performed at 2 to 8 °C during 24 months. The results indicate that Der s 1 adsorption considerably improves when the PBS is reduced or completely removed. However, the variation of AHG showed no significant influence on Der s 1 adsorption. Changes regarding PBS and AHG, and thiomersal removal did not cause alterations in product stability during 24 months. The results demonstrated the consistency of aseptic formulation process for every variant, contributing to define the product design space during pharmaceutical development.