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