Performance analysis of a PEGylation process -Process comparison of a tubular reactor with recirculation to a conventional batch reactor

Abstract: Since the rise of therapeutical proteins, there has been a growing interest in biopharmaceuticals over the years. Research was made to combat various protein weaknesses like fast degradation and low solubility. A discovery in the 1970s suggested that an attachment of polyethylene glycol (PEG) on protein surfaces would solve the specific problems. Today this process is known as PEGylation and is widely used in biopharmaceutical industry. Because of strict pharmaceutical regulations, the PEGylation process is currently performed in batch reactors. These in turn are often connected to Ion Exchange Chromatography (IEC) as a purification step after reaction. However, this type of PEGylation process set-up is not so efficient. Major losses are made due to batch being a non-continuous process and not recirculating unreacted biopharmaceuticals. One suggestion to improve the process is by implementing a tubular reactor system and a recirculation stream. Models were created, one for a batch system and one for the tubular system. Sensitivity analyses were made for every part in the systems to enhance production. Cases were made for each system and then weighed against each other. After selecting best case for each process schematic, the two processes were then compared to each other. The results show a clear improvement of the tubular schematics compared to the batch schematics. Productivity was increased by 71%, from 0.0126 to 0.0216 g/h. The product system yield of was increased by 11%, from 0.43 to 0.46. Waste formation was able to be reduced by 42%, from 0.25 to 0.15. These numbers show a clear potential for tubular reactor systems implemented with recirculation.