Omics tools in accelerated purification process development: Multidimensional fractionation and characterization of crude protein mixtures

Until recently, process development was restricted to a sequential experience based regime. However, new innovativemethods have been developed to perform e.g. up to 96 parallel chromatographic experiments on a Tecan Freedom EVO® robotic workstation, allowing for thermodynamic, kinetic, dynamic binding, and elution studies in an automated, parallelized, and miniaturized mode, which saves time, money, and target molecule. In the era of accelerated time lines to launch new products on the market, traditional experience driven process development seems long outdated. While other fields are front runner in using modern technologies, process development labs in the biotechnological industry are only approaching high throughput techniques, mathematical tools or the computational power available for a few years. Modern high throughput platforms allow the miniaturisation and automation of nearly every unit operation used in biopharmaceutical production. Next to experimental tools for solubility studies, aqueous extractions or IB refolding we will present the complete range of tools for chromatographic process development. Using for example miniaturized chromatographic columns in a 96 well format it becomes possible to either screen chromatographic procedures 8 fold in parallel or to mimic complete multi step chromatographic procedures on an automated HTS platform. In addition the necessity of intelligent screening approaches using mathematical searchalgorithmsand the appropriate high end analytical approaches will be discussed.With such a tool in hand, issues arising in process development can be answered with a limited amount of feedstock and manpower. Case studies will be given using model proteins but also therapeutic targets such as Insulin, mAb and pDNA.