High-throughput, small-scale methodologies are crucial to ensure efficient, rapid and robust development of biological processes. In particular, significant advances have been made in purification process development, allowing parallel experiments to be conducted at the microliter scale, leading to dramatic minimization of resource and material requirements.<br/> <br/>This study describes the application of such high-throughput approaches to enable the bioreactor characterization of a recombinant enzyme process. A high-throughput method for rapid and small-scale purification of bioreactor harvest was required to enable cell culture characterization and small-scale model qualification. Because no affinity chromatography solutions exist for the recombinant enzyme molecule, this effort required a novel approach. To this end, we have developed an automated high-throughput, micro-scale, two-step purification method employing resins used in the at-scale purification process that generated purified product suitable for product quality testing, requiring only milliliters of bioreactor harvest. The high-throughput scale-down Tecan method was developed and optimized to resemble the current purification process to ensure comparable product quality measured using glycosylation profiles. Similar methodologies could be applied for future programs also requiring non-affinity purification processes. In future, additional high-throughput automation techniques could be applied to completely automate this two column small-scale purification process.

High-throughput non-affinity purification methodology to enable bioreactor characterization and small-scale model qualification for a recombinant enzyme

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.