Abstract
inactivation or removal – have to be implemented to assure a high margin of virus safety of these products. Orthogonal mechanisms of virus clearance should be integrated in the manufacturing process in order to inactivate / remove viruses/virus aggregates having been able to escape to a certain degree the reduction capacity of the previous virus clearance step. Virus retentive filters as an orthogonal virus clearance step are frequently implemented in the manufacturing process of biologicals as the virus removal capacity of virus retentive filters is based on size exclusion. Only the size of a virus impacts the removal capacity and not virus properties as enveloped/ non-enveloped or RNA / DNA viruses and their resistance to physiochemical treatment. Viruses larger than the mean pore size of a virus retentive filter are removed from the feed stream and the desired protein – if smaller than the pore size of the filter membrane – will pass the filter and can be collected in the filtrate without / with very low virus contamination. Depending on the filter pore size, virus retentive filters are grouped in large and small virus retentive filters i.e., filters removing large viruses as retroviruses and small viruses as picornaviruses and, especially, parvoviruses. Data of virus reduction factors from 89 publications, resulting in a total of close to 500 virus clearance studies for different viruses, product intermediates and large and small virus retentive filters are assessed. The virus clearance capacity of these filters can depend on the membrane layout and chemistry, the volumetric throughput of product intermediate as well as of buffer flush and transmembrane pressure including pressure/flow interruption and flow decay. These parameters, when disclosed in published data, show filter brand specific differences but, having the above-mentioned parameters for each filter optimised, effective virus removal could mostly be demonstrated in virus validation studies for each filter brand.