Multi-round virus filter integrity test sensitivity.

Virus filtration is becoming increasingly prominent in biopharmaceutical recovery processes as a robust method to remove a broad range of virus types. Increasing batch sizes will require large numbers of individual virus filter elements operating in parallel. Before adopting a more complex strategy for managing the integrity testing of large assemblies of virus filters, it is important to understand the sensitivity of the forward flow diffusion test for a single filter and for multiple filters in a single housing. An approach has been developed to estimate the largest hole that could consistently go undetected in a single filter within a larger assembly of virus filters. The integrity test limited minimum log reduction value (LRV) is determined based on the size of the hole as a function of the number of filters in the housing. This minimum LRV is shown to be largely insensitive to the number of filters within the housing. The likelihood of such damage occurring is expected to be very low. This analysis suggests there is minimal benefit to placing filters in individual housings or to adjusting the test specification to compensate for larger numbers of filters in a given housing.

Binding inhibition of angiogenic factors by heparan sulfate proteoglycans in aqueous humor: potential mechanism for maintenance of an avascular environment.

Aqueous humor is a clear fluid, primarily a blood filtrate, which circulates through the anterior chamber of the eye and bathes the cornea. We explored the possibility that components in the aqueous humor play a direct part in maintaining the avascular environment of the cornea. We report here that heparan sulfate proteoglycan (HSPG) was found in bovine aqueous humor and that it directly inhibits binding of basic fibroblast growth factor and vascular endothelial growth factor to cell-surface heparan sulfate. We demonstrate that this holds true for all heparin binding proteins tested but not for epidermal growth factor, which does not bind heparin. Furthermore, we show, with mathematical modeling, that the concentration of HSPG in aqueous humor (approximately 4 microg/ml), when combined with the clearance of aqueous humor from the eye due to circulation, is sufficient to block the binding of heparin binding growth factors to corneal endothelium. This mechanism suggests a physiological process to control bioavailability of angiogenic growth factors in the cornea.