Regeneration of Capto Core 700 resin through high throughput and laboratory scale studies and impact on production of a SARS‐CoV‐2 vaccine candidate

• Published in: Biotechnology journal Vol. 17; no. 10; pp. e2200191 - n/a
• Main Authors: Konstantinidis, Spyridon, Reinhart, Seth R., Castagna, Christine, Poplyk, Murphy R., Rustandi, Richard R., Flor, Kristen L., Acevedo‐Skrip, Jillian, Thompson, Rachel, Wang, Christopher J., Wang, Sheng‐Ching, Winters, Michael A.
• Format: Journal Article
• Language: English
• Published: Germany 01.10.2022
• Subjects: 1-Propanol; Capto Core; chromatography; CIP; COVID-19 - prevention & control; COVID-19 Vaccines; high throughput; Humans; live virus vaccine; Pandemics; Regeneration; RoboColumns; SARS-CoV-2; scale‐up; Sodium Hydroxide; RoboColumns; chromatography; Capto Core; scale-up; CIP; live virus vaccine; high throughput
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.202200191

During the development of a SARS‐CoV‐2 vaccine candidate, at the height of the COVID‐19 pandemic, raw materials shortages, including chromatography resins, necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core‐shell resin both rapidly and efficiently. Here, the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto Core 700 resin exposed to clarified cell culture harvest (CCCH) of a SARS‐CoV‐2 vaccine candidate produced in Vero adherent cell culture are described. 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 the 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 10 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. Graphical and Lay Summary A chimeric SARS‐CoV‐2 live virus vaccine candidate (VSVΔG‐SARS‐CoV‐2) was purified via Capto Core 700 chromatography. High Throughput (HT) scale column chromatography was deployed to screen cleaning in place (CIP) agents and to test a CIP strategy for 10 cycles. This involved the determination of product purities and yields and of the presence of foulants post CIP in resin extracts from miniature (600 μL) columns between cycles. The results were verified at 20 mL column scale for 10 batches. This work demonstrates that HT scale techniques can lead to effective CIP strategies for chromatography resins.