European Regulatory Approval for a Vaccine

Project Summary: A publicly-held large pharmaceutical company wanted to obtain international approval of a vaccine that had been approved for use in adults and neonates in the US. Rosa created a model that included dose scaling between neonates and adults and also predicted efficacy compared to competitive therapies on the market. Rosa's simulations convinced the European Medicines Agency (EMEA) to approve the vaccine for the European market without additional clinical trials.

Methods: Rosa created a two-compartment population pharmacokinetic (PopPK) model based on time-concentration data of an antibody administered to adults and neonate patients given US-approved dose regimens. Simulations were used to predict time-concentration profiles for dose regimens needed for European approval. Doses were also selected for a non-neonate pediatric group of patients, a new population for which limited data were available using time-variant, weight-based, allometric scaling.

Results:

• Using European dose regimens, therapeutic thresholds were predicted to be achieved in a sufficient portion of the populations, based on model simulations.
• The simulations predicted that the fraction of patients that reached therapeutic threshold was acceptable even with the variations in vaccine potency expected due to differences in commercial and clinical trial preparations.
• Regulatory discussions were focused by the modeling analysis and documentation: the EMEA accepted the modeling predictions with only one minor follow-on question.
• Modeling and simulations were able to identify doses that would show unambiguous efficacy improvements over competitive therapies for future Phase IV investments.