(68e) Innovative Techniques for Planning Experiments Across Mulitple Unit Operations

Many well-established analytical tools and methodologies exist for developing and characterizing a product for manufacture.   However, the application of these tools all too often can fall short of their objective or full potential to gain process understanding – even in the hands of a well trained chemometrician or statistician.  Another essential and uncommon taught skill is in the planning of experiments over the lifecycle of a products development and subsequent manufacture.   The selection of the proper experimental approach and planning activities that precede the actual experimentation are critical to successfully establish process understanding.  The application of proper risk management tools along with established experimental planning principles aide significantly in effectively establishing a product’s experimental development plan.  There are well documented sources that aid in the planning and selection of designed experiments to achieve a desired outcome, especially when looking at a single unit operation at a time.  Yet minimal attention is given to the planning and sequential approach required for experimentation across multiple units operations.  This paper highlights a set of tools and guidelines for assessing technical issues and establishing an appropriate experimental plan when looking across a products manufacturing process.   A pharmaceutical case study involving the experimental strategy taken to develop the design space for a Quality-by-Design filing is provided, and the trade-offs between resource limitations and statistical consequences is included.