Expediting the chromatographic analysis of COVID-19 antibody therapeutics with ultra-short columns, retention modeling and automated method development

Abstract

The COVID-19 pandemic necessitated the emergency use authorization (EUA) of several new therapeutics and vaccines. Several monoclonal antibodies (mAbs) were among those authorized for use, and they have served a purpose to provide passive immunity and to help minimize dangerous secondary effects in at-risk and hospitalized patients infected with SARS-CoV-2. With an EUA submission, scientific data on a drug candidate is often collected near simultaneously alongside drug development. In such a situation, there is little time to allow misguided method development nor time to wait on traditional turnaround times. We have taken this dilemma as a chance to propose new means to expediting the chromatographic characterization of protein therapeutics. To this end, we have combined the use of automated, systematic modeling and ultrashort LC columns to quickly optimize high throughput RP, IEX, HILIC and SEC separations for two COVID-19-related mAbs. The development and verification of these four complementary analytical methods required only 2 days of experimental work. In the end, one chromatographic analysis can be performed with a sub-2 min run time such that it is feasible to comprehensively characterize a COVID-19 mAb cocktail by 4 different profiling techniques within a 1-hour turnaround time.