Chinese hamster ovarian (CHO) cells, commonly used for antibody production processes, are known to endogenously produce retrovirus-like particles (RVLPs). Though non-infectious, safety regulations require downstream processes to demonstrate robust clearance of RVLPs from the product stream. Traditionally, RVLP clearance across the downstream process is demonstrated using scaled-down models spiked with live, model retrovirus (MuLV) and run at the target process conditions. These studies require large amounts of intermediate pools and are performed in a virus laboratory with a suitable biosafety level classification, which can limit the number of conditions evaluated and results in the development of chromatog. steps largely relying upon previous viral clearance knowledge. This work describes the use of purified RVLPs coupled with 96 well plate-based high throughput resin screening tools to define operating spaces for retroviral clearance by chromatog. operations. Since RVLPs are non-infectious and can be quantified by RT-qPCR, a relatively high throughput assay, these studies do not require a biosafety lab and many conditions can be evaluated. Thus, chromatog. steps can be optimized for the clearance of RVLPs and other retroviruses with high throughput screening tools during process development prior to execution of formal virus spiking studies.