ABSTRACT
Biologic drug substance manufacturing processes of commercial products developed before Quality by Design (QbD) were validated based on general knowledge but with limited understanding of the criticality levels of process parameters (PPs) and quality attributes (QAs). Legacy biological/biotechnology products have a wealth of historical data on process parameters, quality attributes, and manufacturing information of various types that from a knowledge management perspective are largely unused over lifecycle. The practical concept of process validation in drug manufacturing has been widely adopted since its origin in the 1970s. Many companies find it easier to postpone improvements to facilities, processes, and analytics, or simply refrain from planning for advancements at all in order to avoid the intricate nature of implementing such changes, especially for products registered in multiple countries. A vial from the working cell bank (WCB) is thawed in culture media. The cell culture is then generated and expanded through successive transfers in shake flasks.
