Table 5.

Selected common methods for virus removal^*

Treatment	Treatment conditions	Advantages	Limitations	Relevant properties
Chromatography	Ion exchange Size exclusion Antibody‐mediated affinity chromatography	Purifies protein Can remove both enveloped and nonenveloped viruses, including HAV and B19V	Virus removal highly dependent on choice of resin, protein solution, and buffers May be highly variable from one virus to another Degree of virus removal may change as resin ages Resin must be sanitized between lots	Resin packing Protein elution profile Flow rate, contact time, and buffer volumes Composition of buffer Number of cycles of resin use
Virus filtration	Filters with pores of approximately 15, 20, 35, and 50 nm	Does not denature or activate proteins when validated production conditions are used67 High recovery of “smaller” proteins such as coagulation F IX	Degree of virus removal depends on the pore size of the filter Removal of small viruses may be incomplete	Pressure Flow rate Filter integrity Protein concentration Ratio of product volume to filter surface area Buffer composition

* Adapted from the World Health Organization.13