Plasma fractionation processes used in the manufacture of albumin, immunoglobulins, factor-VIII concentrate, factor-IX concentrates, fibrinogen and thrombin all contain steps which may be capable of removing causative agents of human TSEs.
Within Australia, there has been a gradual increase in the incidence of transmissible spongiform encephalopathy over the three-decade period 1970 through 1999, peaking in 1999 at 1.4/million/year for sporadic Creutzfeldt-Jakob disease. This increase is believed secondary to improved case ascertainment. Variant Creutzfeldt-Jakob disease was not identified during this period. Age- and sex-adjusted comparisons showed a decline in incidence rates in the elderly in both sexes, usually from age 74 years. Death certificates were a useful but imperfect method of case detection.
Background and Objectives: To identify if any process steps used in plasma fractionation may have a capability of removing agents of human transmissible spongiform encephalopathy (TSE). Materials and Methods: Sixteen fractionation steps were investigated separately by adding a preparation of hamster adapted scrapie 263K to the starting material at each process step and determining the distribution into resultant fractions of protease–K–resistant (abnormal) prion protein by Western blot analysis. Results: A number of process operations were found to remove abnormal prion protein to the limit of detection of the assay. These were cold ethanol precipitation of fraction IV (log reduction, LR, ≥3.0) and a depth filtration (LR ≥4.9) in the albumin process; cold ethanol fraction I+III precipitation (LR ≥3.7) and a depth filtration (LR ≥2.8) in the immunoglobulin processes and adsorption with DEAE–Toyopearl 650M ion exchanger (LR ≥3.5) in the fibrinogen process. In addition, a substantial degree of removal of abnormal prion protein was observed across DEAE–Toyopearl 650M ion exchange (LR = 3.1) used in the preparation of factor–VIII concentrate; DEAE–cellulose ion exchange (LR = 3.0) and DEAE–sepharose ion exchange (LR = 3.0) used in the preparation of factor–IX concentrates and S–sepharose ion exchange (LR = 2.9) used in the preparation of thrombin. Conclusions: Plasma fractionation processes used in the manufacture of albumin, immunoglobulins, factor–VIII concentrate, factor–IX concentrates, fibrinogen and thrombin all contain steps which may be capable of removing causative agents of human TSEs.
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