(299d) The Heartburn Associated with Implementing Quality by Design Principles

Many challenges exist with implementation of the various aspects of Quality by Design. Challenges include the integration of newer approaches to development and technology transfer into facilities running long-established processes developed and installed using more traditional approaches. Additionally, Quality Systems and procedures that have long been in place require modernization to allow for flexible processing approaches and the use of advanced control mechanisms utilizing PAT. Lastly, understanding the potential changes to regulatory commitments and the resulting changes to notification requirements, and the potential cost/benefits to the pharmaceutical industry is not yet fully understood and tested.

While differences in approaches are clearly apparent between various pharmaceutical companies, a more difficult challenge exists when differing opinions and interpretations exist within the same company across different divisions. Small molecule interpretations and drivers may be significantly different than those in the large molecule areas. Differences in drug product and drug substance manufacturing, and the inherent differences in the unit operations, starting material variability, control systems, ability to build representative models, and the ability to perform designed experiments at representative scales also poses some significant barriers and challenges to the implementation of Quality by Design Principles.