Implementation of a 20‐nm pore‐size filter in the plasma‐derived Factor VIII manufacturing process

Abstract

The virus-clearance efficiency of the FVIII product, CROSS EIGHT M, was markedly increased, in particular against small non-enveloped viruses, by changing the virus filter pore size from 35 nm to 20 nm. It was possible to implement the 20-nm pore-size filter without variation of the biochemical properties or a serious loss of FVIII.

Hepatitis E virus and the safety of plasma products: investigations into the reduction capacity of manufacturing processes

“…The validated downscaled model of the nanofiltration step used the fully automated filtration equipment recently reported . Approximately 30 or 60 mL of 1:11 (for rHEV) or 1:60 (for wtHEV from swine feces) spiked process intermediate, respectively, was applied to 0.1‐µm prefilters (Durapore PVDF, Merck Millipore Corp., Darmstadt, Germany) followed by 0.001‐m 2 20‐nm virus filters (Planova, Asahi Kasei Corp., Tokyo, Japan), similar to that described …”

Non-enveloped virus reduction with quaternized chitosan nanofibers containing graphene

“…27 They are most effectively removed by 20 nm pore-size nanofilters, but these filters are known to foul easily and have high pressure drops. 11,42,43 Because of the difficulty of removing and inactivating this virus, we use it as a model of virus reduction in solution. The ability to remove a virus with a membrane that has pores that are orders of magnitude greater in size has the potential to greatly improve current virus reduction techniques.…”

Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein

“…Reducing the pore size in nanofiltration is known to greatly enhance the effectiveness of viral clearance without affecting purified FVIII [36]; the small pore size (15 nm) of the Planova 15N virus filter provides an effective barrier for a wide range of largesize impurities. In the current study, the Planova 15N filter provided an extremely stringent level of clearance providing a total reduction factor !8.3 log 10 for each of the model viruses tested and >15 log 10 clearance of retroviruses.…”