QbD Strategies Employed for a Biopharm Fermentation Process: A Customer’s Perspective

The use of QbD principles in the development of any process should help to ensure that the appropriate outcome is achieved.  However, translating the needs of the patient into acceptable outcomes of fermentation processes and relevant control strategies can be challenging and requires input from many different groups. This presentation will discuss the QbD strategy and tools that were used in developing and characterizing a Saccharomyces cerevisiae fermentation process and product control strategy, with focus on determining acceptable ranges and translation of the process knowledge into effective controls.  Knowledge of the product and expected changes in product quality in the downstream process were used to identify acceptable ranges for in-process attributes.  Risk assessments were used to rank process parameters according to their potential impact on the output attributes.  Small-scale studies were conducted to verify impact ratings and establish acceptable operating ranges using a multivariate Bayesian predictive approach. Further understanding was achieved through use of exometabolome analysis as evidence of hypoxia during up-scaling of the process.  The total process knowledge was then used to develop an initial product control strategy that was communicated to internal manufacturing groups and health authorities. These controls were translated to manufacturing procedures and are monitored as part of continued process verification to ensure the fermentation process delivers the appropriate product quality.