(533a) Drug Product Model Design, Development, Qualification, and Maintenance in a QbD Framework

Model development and implementation is a core principle to employing a QbD approach in drug product design and process scale-up. The advantages in taking this approach are realized through the ease of visualization or mathematical expression of data sets for greater process understanding, which leads to clear decision making and results in superior product quality. There are several model types that can be developed and used at every stage in the QbD process.  A favored approach is to begin with the end in mind by outlining up front a clear plan toward model design and development for the drug product process, considering how each model will be used, limitations, assumptions, qualification, and maintenance. The experimental approach to the development of each model should consider the type of model (mechanistic or empirical), selected variables, scale dependency and relationship to the overall drug product process. Once a model has been developed, steps are needed toward implementation through qualification of the model and evaluating uncertainty in predictions. Finally, for models selected for use in commercial manufacture, a maintenance plan is needed to support product life cycle, allowing model updates as needed. In this presentation, representative examples will be provided using these principles that have been used to support drug product filings.