Use of Modeling and Simulation to Inform the Development of Monoclonal Antibodies to Treat Moderate-to-Severe Asthma: A Retrospective Review of EMA Centralized Procedure From 2014 to 2024.

We present here a repository of key regulatory questions answered in centralized procedures and evaluate the place of modeling and simulation in marketing authorization process for biologics approved for the treatment of moderate-to-severe asthma from 2014 to 2024. This was done consistently with the ICH M15 recommendations and the ERAMET project that consistently aim to define the framework for assessment of model informed drug development evidence to inform decision-making. We carried out a search for marketing authorization applications for the five approved monoclonal antibodies in the treatment of asthma from 2014 to 2024. We translated the information into essential regulatory questions and classified the questions based on the level of the questions and their granularity. Credibility activities were performed by applying the credibility framework of the ICH M15 guidelines to questions answered by modeling and simulation methods. A total of 190 questions were extracted including 74 questions related to efficacy, 86 to safety, and 30 questions related to pharmacokinetics. The proportion of questions answered oscillated between 51% and 65% for each drug. Modeling and simulation methods were used to answer 25% of the questions. These methods are predominantly used to address pharmacokinetics questions, with 60% of these questions answered in at least one marketing authorization application using these methods. Credibility matrices were fulfilled for questions answered by modeling and simulation methods. We identified the types and roles of modeling and simulation approaches used in the development of monoclonal antibodies for treat moderate-to-severe asthma approved from 2014 to 2024.