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Mechanistic insights into viral clearance during the chromatography steps in antibody processes by using virus
Rachel Dyer1, Yuanli Song1, Jie Chen1
1Biologics Development, Bristol-Myers Squibb, Devens, Massachusetts, USA.
Abstract:
Viral safety is required for biological products to treat human diseases, and the burden of inactivation and or virus removal lies on the downstream purification process. Minute virus of mice (MVM) is a nonenveloped parvovirus commonly used as the worst-case model virus in validation studies because of its small size and high chemical stability. In this study, we investigated the use of MVM-mock virus particle (MVP) and bacteriophage ΦX174 as surrogates for MVM to mimic viral clearance studies, with a focus on chromatography operations. Based on structural models and comparison of log reduction value among MVM, MVP, and ΦX174, it was demonstrated that MVP can be used as a noninfectious surrogate to assess viral clearance during process development in multiple chromatography systems in a biosafety level one (BSL-1) laboratory. Protein A (ProA) chromatography was investigated to strategically assess the impact of the resin, impurities, and the monoclonal antibody product on virus removal.
Insights
Minute virus of mice (MVM) mock virus particles (MVP) and bacteriophage ΦX174 are effective noninfectious surrogates for viral clearance studies. MVP can be used in biosafety level one (BSL-1) laboratories for chromatography process development, ensuring biological product safety.
Area of Science:
- Biopharmaceutical Manufacturing
- Process Development
- Viral Safety
Background:
- Ensuring viral safety is critical for biological products.
- Downstream purification processes are responsible for viral inactivation and removal.
- Minute virus of mice (MVM) is a robust model virus for clearance studies due to its stability and size.
Purpose of the Study:
- To evaluate MVM-mock virus particle (MVP) and bacteriophage ΦX174 as surrogates for MVM in viral clearance studies.
- To assess the utility of MVP in chromatography operations within a biosafety level one (BSL-1) laboratory.
- To investigate the impact of Protein A (ProA) chromatography on viral removal.
Main Methods:
- Comparative analysis of log reduction values (LRVs) between MVM, MVP, and ΦX174.
- Utilizing structural models for surrogate selection.
- Performing viral clearance studies across multiple chromatography systems.
- Investigating Protein A chromatography with varying resins, impurities, and monoclonal antibody products.
Main Results:
- MVP demonstrated efficacy as a noninfectious surrogate for MVM in viral clearance assessments.
- MVP and ΦX174 showed comparable performance to MVM in structural models and LRV comparisons.
- MVP can be safely used in BSL-1 laboratories for process development.
- Protein A chromatography's impact on viral removal was strategically assessed.
Conclusions:
- MVP is a suitable noninfectious surrogate for MVM, enabling viral clearance studies in BSL-1 settings.
- The use of MVP simplifies and enhances the safety of viral clearance validation in bioprocessing.
- Chromatography operations, particularly Protein A, play a significant role in viral clearance strategies.
