Predicting Viral Clearance: Utilizing A Non-Infectious MVM Surrogate During Downstream Development

Viruses can arise during the manufacture of biopharmaceuticals through contamination of exogenous viruses or endogenous expression of viral sequences. Regulatory agencies therefore require “viral clearance” validation studies for each biopharmaceutical prior to approval. These studies demonstrate the manufacturing process’ ability at removing or inactivating virus and are conducted by challenging scaled-down manufacturing steps with a “spike” of live virus. These studies are conducted in BSL-2 facilities and are costly. Due to these hurdles, process knowledge pertaining to viral clearance is limited during development and  characterization. The use of an accurate, economical and quantifiable non-infectious viral surrogate would enable downstream purification scientists to study viral clearance throughout process development.

A non-infectious Minute Virus of Mice—Mock Virus Particle (MVM-MVP) was generated by MockV Solutions, Inc. for use as an economical spiking surrogate. Discussed here are results from three studies. First, an AEX DOE study in which MVM-MVP clearance was compared to MVM and then used to generate a model for mapping design space. Second, a series of IEX high throughput screening experiments in which in-process vaccine material was spiked with MVM-MVP and processed through robo-columns under conditions of increased conductivity. Third, a comparative MVM vs. MVM-MVP clearance study utilizing AAVX resin (Thermo Fisher Scientific) in a downstream AAV process. The results from these studies demonstrate the value of utilizing this non-infectious tool for process development and characterization.