Regeneration of Capto™ Core 700 Resin through High Throughput and Laboratory Scale Studies and Impact on Production of a SARS-CoV-2 Vaccine Candidate (preprint)

ABSTRACT

The biopharmaceutical industry is capable of rapid responses in the face of unprecedent challenges, such as the COVID-19 pandemic; safe and efficacious vaccines were developed in record times. However, additional hurdles, including raw materials shortages, need be overcome to improve further the industry’s agility. During the development of a SARS-CoV-2 vaccine candidate, such supply limitations necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core-shell resin both rapidly and efficiently. This is a challenging task with its complexity depending on the nature of the resin and the composition of the feed stream. Here, we describe the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto™ Core 700 resin exposed to clarified cell culture harvest of a SARS-CoV-2 vaccine candidate produced in Vero adherent cell culture. The best performing conditions, comprised of 30% n-propanol and ≥0.75 N NaOH, were deployed in cycling experiments, completed with miniature chromatography columns, to demonstrate their effectiveness. The success of the CIP strategy was ultimately verified at laboratory scale. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. It is shown that the implementation of the CIP strategy enabled the re-use of the Capto Core 700 resin for up to ten cycles without any negative impact on the purified product. Hence, the strategic combination of HT and laboratory scale experiments can lead rapidly to robust CIP procedures, even for a challenging to clean resin, and thus help to overcome supply shortages.