Validation of adequate virus clearance is critical in order to obtain FDA approval for a manufacturing process. Clearance can be due to inactivation or removal from the process stream. During the purification, manufacturers of monoclonal antibodies must demonstrate reduction of 103 to 105 or more virus particles than is estimated in a single dose equivalent of the unprocessed bulk. Depending on the antibody titer, estimates of the number of virus particles in a single dose equivalent could be as high as 1010 to 1015 retrovirus-like particles per ml. In addition to the removal of adventitious virus, using model parvovirus is required. Today unit operations such as virus filtration are frequently used to validate virus clearance. Virus filtration is a size exclusion based virus clearance method and is conducted industrially in dead end mode. Membrane performance is shown to be affected by feed pH, ionic strength and feed buffer components. In this work, one of the FDA required model viruses, minute virus of mice (MVM) was spiked to evaluate the filtration performance of BSA protein using commercially available virus filters. The effects of feed conditions including buffer, pH and ionic strength on membrane performance and virus clearance were elucidated. Moreover, the interactions and possible associations among virus particles, proteins and membrane materials modulated by the feed conditions were investigated using confocal imaging studies.

The effects of buffer condition on viral clearance of model proteins

255th National Meeting (2018)

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