S15: Case study: QbD microbial process characterization and validation

This case study will discuss the process characterization program for a recombinant protein produced in E. coli using a Quality by Design approach. The tools and experimental methodology will be discussed including: 1) risk-based assessment of process parameters for inclusion in the experimental design; 2) statistical design of experiment (DOE) to evaluate parameters for impact on product quality; 3) evaluation of DOE feedstock’s subsequent downstream clearance of product- and process-related impurities for confirmation of the proposed operating space; 4) evaluation of DOE model results against product quality targets; 5) univariate studies to extend proven acceptable ranges (PARs) to support future investigations of manufacturing excursions; and 5) the identification of critical process parameters.