(158c) The Effects of Filtration Condition on Virus Clearance

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 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 and used to investigate the effects of feed condition including pH, buffer and ionic strength on membrane performance and virus clearance using commercial virus filters in the presence and absence of model proteins. The interactions and possible associations among virus particles, model proteins and membrane materials modulated by the feed conditions were investigated. Their effects on membrane filtration performance and MVM clearance were elucidated.