Lee, J. S. Z., Nguyen, T. D., Zheng, Z. Y., Zhang, W., & Liu, D. (2024). Real‐Time Adaptive Inline Acidification Enhances Continuous pH Control for Viral Inactivation. Biotechnology Journal, 19(11). Portico. https://doi.org/10.1002/biot.202400456
Abstract:
Existing low pH viral inactivation methods for continuous downstream processing of biologics typically rely on predictive models to estimate the necessary pH adjustments. However, these methods are of limited use during the process development stage due to the dynamic nature of capture chromatography, where batch variations can alter the eluted protein titer. This study introduces an inline viral inactivation system (IVIS) that utilizes real‐time adaptive control and inline sensor readings to precisely regulate the pH manipulation for inline acidification and continuous viral inactivation. The IVIS, which includes a coiled flow inversion reactor (CFIR), is integrated with a multicolumn capture chromatography system to demonstrate a fully continuous process from protein capture chromatography to inline pH manipulation. The system achieved precise inline pH manipulation within ±0.15 and a narrow residence time distribution of 13.5 min with a relative width of 0.7. The introduction of real‐time inline pH manipulation with the IVIS signifies a notable advancement in managing critical process parameters (CPPs) and ensuring consistent product quality across varied production environments for continuous downstream bioprocessing.
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Publisher Copyright
Funding Info:
This research is supported by core funding from: Bioprocessing Technology Institute, A*STAR
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Description:
This is the peer reviewed version of the following article: Lee, J. S. Z., Nguyen, T. D., Zheng, Z. Y., Zhang, W., & Liu, D. (2024). Real‐Time Adaptive Inline Acidification Enhances Continuous pH Control for Viral Inactivation. Biotechnology Journal, 19(11). Portico. https://doi.org/10.1002/biot.202400456, which has been published in final form at https://doi.org/10.1002/biot.202400456. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.