Digital Twins for scFv Production in Escherichia coli

Quality-by-Design (QbD) is demanded by regulatory authorities in biopharmaceutical production. Within the QbD frame advanced process control (APC), facilitated through analytical technology (PAT) and digital twins (DT), plays an increasingly important role as it can help to assure stay within predefined proven acceptable range (PAR).This ensures high product quality, minimizes failure step towards a real-time-release testing (RTRT) that could accelerate time-to-market of drug substances, which becoming even more light dynamical pandemic situations. The approach exemplified on scFv manufacturing Escherichia coli. Simulation results from are compared experimental data found be accurate precise. Harvest achieved tangential flow filtration followed release pressure homogenization subsequent clarification filtration. Digital membrane processes show shear rate transmembrane significant parameters, line with data. Optimized settings were applied 0.3 bar 11,000 s?1. Productivity chromatography steps 5.3 g/L/d (Protein L) 2167 (CEX) final concentration was 8 g/L. Based twin results, optimized schedule developed decreased purification time one working day, factor-two reduction conventional schedule. This work presents basis for future studies automation biologics production microbials regulated industries.