Innovative chromatography design combined with high-throughput analytics to streamline therapeutic purification

Background: Chromatography unit operations now accounts for almost 80% of drug development manufacturing costs and selecting the optimum process operation set-points typically involves laborious experimental work involving large amounts of expensive resin and requires high volumes of biotherapeutic proteins.

Goal: The primary objective of developing and modelling an automated scale-down chromatography system with in-built analytics to simplify product purification and speed up drug development timelines

Project objective: The objective of this project will be to design, print, model and experimentally validate a scale-down 3-D printed chromatography column with unique internal flow paths. The device will enable the evaluation of a wide range of critical process parameters such as dynamic binding capacity, load and elute pH conditions and different resin types all within a single experimental pass whilst requiring a log-fold reduction in sample material. Although scale-down chromatography systems have been built in the past [1] one of the key aspects of this approach will be the integration of a novel high-throughput analytics (i.e Raman spectroscopy device) enabling near-real time information to predict the key critical quality attributes e.g. aggregation and fragment concentrations. This proposal will take advantage of the highly sophisticated 3-D printer facilities [2] and fundamental expertise held at UCD supported by advanced analytics and expertise within NIBRT. In addition to leveraging UCL's domain expertise in therapeutic manufacturing and utilising available equipment to support the high-throughput analytics[3] and experimentation within this proposal.