Viruses can arise during the manufacture of biopharmaceuticals through contamination or endogenous expression of viral sequences. Regulatory agencies require "viral clearance" validation studies for each biopharmaceutical prior to approval. These studies aim to demonstrate the ability of the manufacturing process at removing or inactivating virus and are conducted by challenging scaled-down manufacturing steps with a "spike" of live virus. Due to the infectious nature of these live viruses, "spiking studies" are typically conducted in specialized biological safety level-2 facilities. The costs and logistics associated with these studies limit viral clearance analysis during process development and characterization. In this study, a noninfectious Minute Virus of Mice-Mock Virus Particle (MVM-MVP) was generated for use as an economical small virus spiking surrogate. An immunoglobin G containing solution was spiked with live MVM or MVM-MVP and processed through Planova nanofiltration units. Flux decay data was collected and particle reduction values were calculated from TCID50 and Immuno-qPCR analysis. The data indicated comparable filtration performance and particle reduction between infectious MVM and noninfectious surrogate, MVM-MVP. This proof of concept study suggests the feasibility of utilizing MVPs for predictive size-based viral clearance assessments during process development and characterization as an alternative to homologous infectious virus. (C) 2018 American Institute of Chemical Engineers