In these boxes, numbers correspond to cleaning conditions, also shown on the x‐axis of (A), and asterisks denote replicated experiments using previously tested cleaning conditions. In (B–H), boxes above each gel denote the samples tested per lane and gel. Biotechnology Journal published by Wiley-VCH GmbH.Įvaluation of 36 cleaning in place conditions, implemented by applying up to three different cleaning agents in three sequential steps, each deployed at the end of a purification run to generate the chromatography flowthrough product pool (ChromP) from clarified cell culture harvest (CCCH) using RoboColumns: (A) Total signals from optical absorbance measurements at 280 nm from fractions collected during the loading, washing, application of cleaning in place steps 1–3, and post‐CIP flushing the columns (FT, Wash, CIP1, CIP2, CIP3, and PCIP, respectively) per cleaning condition (B–H) SDS‐PAGE analysis of resin extracts collected at the end of each CCCH purification and deployment of the cleaning conditions. 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.ĬIP Capto Core RoboColumns chromatography high throughput live virus vaccine scale-up. 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. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. The success of the CIP strategy was ultimately verified at the laboratory scale. 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. 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. 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.

Capto core 700