Removal of TSE agent from plasma products manufactured in the United Kingdom

Abstract

All the processes showed a substantial capacity to remove the TSE agent. However, this was more limited for the intermediate purity factor VIII 8Y which included fewer manufacturing steps.

A prion reduction filter does not completely remove endogenous prion infectivity from sheep blood

“…At present, the only peer‐reviewed data available on the use of the P‐CAPT filter relate to its application for removal of exogenous and endogenous infectivity associated with 263K hamster scrapie. Studies using hamster brain homogenate spiked into a full unit of human LR‐RBCs indicated that processing using the P‐CAPT filter resulted in approximately 3‐log reduction in infectivity . However, it has been shown that as little as 200 µL of intravenously (IV) administered blood can transmit infection between scrapie‐infected sheep, despite very low infectious titers estimated by intracerebral inoculation of blood into transgenic mice expressing sheep PrP, while the equivalent minimal infectious dose of brain‐derived scrapie for sheep by the IV route is approximately 1000 times greater .…”

“…One novel approach is prion filtration, which aims to remove abnormal PrP from blood by selective binding to affinity ligands or resins, using devices such as the MacoPharma P‐CAPT filter, the Pall Corporation Leukotrap filter, and the Asahi KASEI combination filter . Many of the studies evaluating the efficacy of these prion reduction filters have used brain spiked into blood or blood components as a way to assess the extent of prion removal. However, this approach may not replicate the effects of filtration on endogenous infectivity in blood.…”

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

“…Metals have been investigated in relation to conversion of PrP to a protease resistant form. Although copper can cause increased protease resistance, it has not been linked to the formation of PrP Sc (Quaglio et al, 2001;Roberts et al, 2013) but has been shown to accelerate its formation when PrP Sc is already present (McKenzie et al, 1998). In contrast, manganese has been suggested to cause spontaneous PrP Sc formation (Brown et al, 2000) and manganese chelation has been shown to decrease PrP Sc present in infected rodent brains (Brazier et al, 2010).…”

Products Used to Treat Hemophilia: Plasma‐derived Coagulation Factor Concentrates

“…It is therefore reassuring that plasma fractionation techniques appear quite fortuitously to eliminate substantial amounts of prions [30]. Cost alone should certainly not be the deciding factor when choosing products.…”