S64: Impact of Regulatory Guidances on Biopharmaceutical Cell Culture

The expectations for commercial biopharmaceutical cell culture are changing.  To improve patient safety and process reliability, biopharmaceutical cell cultures for therapeutic proteins now have an enhanced level Regulatory oversight that requires deep process understanding and better process designs. The compliance with Regulatory Guidelines is driving science-based and risk-based evaluations, which link product quality attributes to medicinal safety and efficacy.   Improvements in analytical methods for therapeutic proteins and a greater focus on Quality by Design have brought biopharmaceuticals to a new level of process control and ongoing monitoring.   In recent years, Guidelines have opened the door to the utilization of formal prior knowledge about product types, particularly therapeutic monoclonal antibodies and related proteins.    When prior knowledge is combined with well designed experiments, then justification for any particular design space become clearer and process control strategies are easier to communicate to Regulatory authorities.  Finally, the validation of cell-culture processes is no longer a simple matter of running some validation studies under pre-defined protocols.  The realm of process validation has been expanded to include three stages: Process Design, Process Qualification and Continued Process Verification.  The new world of Process Validation ensures cell-culture process parameter validity all the way from the developmental design, thru pre-approval qualification studies, into on-going collection of operational performance data that reveals sources of process variation within an overall control strategy framework.  The net result will be enhanced safety for patients, throughout the life-cycle of cell-culture-based biopharmaceutical products.