(577d) Specifications By Design: Framework for Setting Specifications to Maximize Flexibility and Meet Design Requirements

Authors: 
Viswanath, S. K., Eli Lilly & Co.
Vaidyaraman, S., Eli Lilly and Company
Traditionally, specifications for API starting materials, intermediates and final API are set based on historical data, process capability and limit of quantitation/detection. The flexibility of the process is then determined based on using specification as constraints. Instead of the sequential approach, there is potential for a better outcome by integrating specification setting with process flexibility and design requirements. In this talk, we propose the framework of “Specifications by Design” where the objective is to set specifications for API starting materials, intermediates and final API to balance process flexibility with specification flexibility while meeting design requirements. We will illustrate the framework with few examples: (1) Setting residual solvent specifications for API to balance the flexibility of a key unit operation in the process and the flexibility of specification while meeting the design requirement of desired product performance (2) Setting a isomer impurity specification to balance specification flexibility and meet business design requirements of yield/API cost.