Mechanistic modeling based process analytical technology implementation for pooling in hydrophobic interaction chromatography.

摘要: A major challenge in chromatography purification of therapeutic proteins is batch-to-batch variability with respect to impurity levels and product concentration the feed. Mechanistic model can enable process analytical technology (PAT) implementation by predicting impact such variations thereby improving robustness resulting controls. This article presents one application mechanistic hydrophobic interaction (HIC) as a PAT tool for making robust pooling decisions clearance aggregates monoclonal antibody (mAb) therapeutic. Model predictions were performed before actual experiments facilitate feedforward control. The approach has been successfully demonstrated four different feeds varying aggregate (3.84%-5.54%) feed (0.6 mg/mL-1 mg/mL). pool consistently yielded 1.32 ± 0.03% vs. target 1.5%. comparison traditional involving column fractionation proposed indicates that results achievement satisfactory purity (98.68 ± 0.03% based controlled 98.64 ± 0.16% offline pooling). © 2018 American Institute Chemical Engineers Biotechnol. Prog., 35: e2758, 2019.