(569e) Use of Design of Experiments (DoE) and Empirical Modeling in Liquid-Liquid Extraction Design Space Development

A robust quality control strategy for the production of active pharmaceutical ingredients (APIs) and related intermediates is an essential element of pharmaceutical process development. Although numerous examples for reactions and crystallizations exist in the literature, techniques employed during ubiquitous operations such as liquid - liquid extraction are limited. This presentation will address that gap by reviewing the creation of a control strategy to purge a key impurity from an intermediate via liquid - liquid extractions.  An important element of laboratory studies proved to be application of multiple rounds of fractional factorial design of experiments (D o E). The collected data was used to both construct and verify an empirical model and later construct a response surface. A five factor, multivariate design space was identified and formed the basis for the quality control strategy. The strategy has been successfully demonstrated in numerous pilot plant scale campaigns and validated at commercial manufacturing.