An Overview of the Role of Mathematical Models in Implementation of Quality by Design Paradigm for Drug Development and Manufacture

The Quality by Design (QbD) paradigm for drug development and manufacture is a science- and risk-based approach that begins with predefined objectives for meeting the desired clinical performance and emphasizes product and process understanding and process control. In the QbD paradigm, mathematical models can be utilized at every stage of drug product development and manufacturing. Examples include risk assessment to identify potential parameters that can affect the finished product quality, design space development for process operation, monitoring and control of the process during commercial manufacturing, and finally support of continual improvement of product quality. The aim of this chapter is to use examples from literature to describe various modeling approaches useful for the implementation of the QbD paradigm and to discuss some general scientific considerations for implementation of models throughout the product life cycle.