(677d) Defining Design Space for Biotech Products: Case Study of Pichia Pastoris Fermentation

The concept of ?design space? has been proposed in the ICH Q8 guideline and is gaining momentum in its application in the biotech industry. It has been defined as ?The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality.? This paper presents a stepwise approach for defining design space for a biologic product. A case study, involving P. pastoris fermentation, is presented to facilitate this. First, risk analysis via Failure Modes and Effects Analysis (FMEA) is performed to identify parameters for process characterization. Second, small-scale models are created and qualified prior to their use in these experimental studies. Third, studies are designed using Design of Experiments (DOE) in order for the data to be amenable for use in defining the design space. Fourth, the studies are executed and the results analyzed for decisions on the criticality of the parameters, as well as, on establishing design space. For the application under consideration, it is shown that the fermentation unit operation is very robust with a wide design space and no critical operating parameters. This approach can be extended to other biotech unit operations and processes that can be scaled down and characterized at small scale.