_Clearance of TSE Infectivity in PlasmaderiTSE感染血浆德里实验间隙课件.ppt

Experimental Clearance of TSE Infectivity in Plasma-derived FVIII Products TSE Advisory Committee December 15, 2006 Dorothy Scott, M.D. Office of Blood Research and Review/CBER Questions to the Committee 1. Based on available scientific knowledge, please discuss whether a minimum TSE agent reduction factor, demonstrated using an exogenous (spiking) model in scaled-down manufacturing experiments, can be identified, that would enhance vCJD safety of the products. a. If yes, what TSE agent reduction factor is most appropriate? 2. If the Committee identifies a minimum TSE reduction factor that would enhance vCJD safety what actions should FDA consider in cases when a licensed pdFVIII has a lower reduction factor: Labeling that would differentiate the higher clearance products from other products; Recommending addition of TSE clearance steps to the manufacturing method; Performance of TSE clearance experiments using endogenous infectivity models; Any other actions? Exogenous Clearance Studies – Spiking Material “Ideal” spiking material Physically/chemically replicates blood infectivity Easy to prepare, widely available High-titer material Committee discussion 9/18/06 (What would be optimal spiking material and its preparation?) Brain subfractions may be better than whole homogenate Can higher titer infectivity fractions relevant to blood infectivity be generated? LDL//VLDL bound fraction from plasma Other purification methods (e.g. solublized homogenate) “There is no pending resolution of the physical form of [blood] infectivity” Spiking studies use human plasma and intermediates - highly process-relevant (animal plasma may fractionate differently) Exogenous Experiments – Selection of TSE strains and animal model (TSEAC discussion 9/18/06) Most relevant strains may be BSE/vCJD-related, but well-characterized and practical vCJD model in rodents not yet available Transgenic mice (PrP-transgenic for specific TSE strain) may provide greater sens