(264d) QbD in Development and Commercial Manufacture

Quality by Design (QbD) elements are an integral component of product development and regulatory submissions, enabling continual improvement throughout the product lifecycle. QbD can provide a systematic approach in which prior knowledge from platform technologies is leveraged to focus resources on understanding variability critical to a specific product and/ or process. Companies decide on the extent to which to invest in QbD based on the stage of development and product and/or process risk and expand the use of QbD principles during the development process. Design spaces can be established for processes initially identified as high risk as that knowledge is used to establish appropriate process and input material controls for commercial operations. Raw material monitoring plans that support continual improvement can support expanded material attribute ranges based on a robust understanding of their interaction and impact on product quality. Process analytical technology (PAT) is often deployed primarily during development to rapidly understand sensitivity to variability and establish appropriate controls that are subsequently used during production, however PAT has been successfully implemented globally for release, in limited cases.

Regulatory flexibility as a result of QbD development and registrations has not been fully realized, however with continuous manufacturing this is expected to change. Design spaces across integrated unit operations can be established on commercial equipment without requiring extensive input materials and time. This provides a comprehensive understanding of the process sensitivities, the appropriateness of the control strategy and the justification for regulatory and operational flexibility. Furthermore, the shift towards performance-based approaches for analytical methods and models where the focus is on control of the output rather than the input can provide additional flexibility.

The objective of this presentation is to provide examples of how QbD elements and PAT are used to develop a robust process and how continuous manufacturing can fully utilize QbD in development and commercial manufacture allowing for potential regulatory flexibility.