Results using a BSE-derived agent suggest that vCJD infectivity should be substantially removed from immunoglobulin G (IgG) solutions by Fraction I+III precipitation and Seitz KS80 depth filtration. The three different process steps examined acted in a complementary manner to one another when operated in series. However, the data demonstrated that it would be inappropriate to add together the reduction factors that had been derived for each step in isolation.
This new single-use, disposable PrP(Sc)-harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG, in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.
The behavior of the transmissible spongiform encephalopathies (TSE) causing agent denominated "prion protein" in anaerobic sludge (biogas reactor) was assessed with incubation tests. A widely applied screening method for BSE in cattle on the basis of the Western blotting protocol was adapted to detect the Proteinase K resistant, scrapie-form prion protein (PrPSC). As PrPsc source homogenized TSE infected brain tissue of animals late in the clinical phase of disease was taken (301V/VM mouse-BSE; bovine BSE and 22A/SV mouse-scrapie). The incubation under mesophilic conditions did not show any significant reduction of the PrPsc titer. Under thermophilic conditions contradictory results were obtained. The reduction time of PrPsc in water was equal to or longer than the PrPsc reduction time in anaerobic sludge. In comparison, with sterilized (121 degrees C, steam pressure) or poisoned (sodium azide, 1% w/v) sludge used as incubation matrix a much shorter time resulted until no prion protein could be detected.
Results using a BSE-derived agent suggest that vCJD infectivity would be substantially removed by the ion-exchange process used in the preparation of fibrinogen and factor VIII concentrate. Although 301V infectivity remained bound to the ion-exchange matrix following elution of factor VIII, this appeared to be eliminated by the procedure used for cleaning the ion-exchange media after each use.
Evidence is emerging that suggests that the protease-resistant isoform (PrP(sc)) of the normal cellular prion protein (PrP(c)) can be detected in the blood and urine of animals and humans with transmissible spongiform encephalopathies (TSEs). The production of the human menopausal and recombinant gonadotrophin preparations for use in ovarian stimulation protocols in fertility treatment is one area where the pharmaceutical industry needs to be vigilant and take appropriate steps to ensure that the safety of such drugs remains as high as ever. The recombinant preparations utilize fetal calf serum or other animal sera or proteins as part of a culture medium during production. Human urinary-derived menotrophin preparations are exposed to the theoretical risk of infection from menopausal donors of urine. Nevertheless, the failure to demonstrate irrefutably infectivity following intracerebral inoculation with urine from TSE-infected hosts suggests that the risk associated with products derived from urine is merely theoretical. Despite the paucity of evidence to date and its relevance to the infectious spread of TSEs, it is important that robust measures are implemented to either remove or inactivate PrP(sc) in order to minimize contamination. Validation of each production process is required to assess the likelihood of contamination.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.