beta-propiolactone/ultraviolet irradiation: a review of its effectiveness for inactivation of viruses in blood derivatives.

The efficacy of combined beta-propiolactone/ultraviolet irradiation (betaPL/UV) for inactivation of hepatitis B virus in labile blood derivatives has been reviewed. The initial evaluations of these procedures were hampered by inadequate process control that resulted in excessive protein denaturation; furthermore, adequate evaluation of process efficacy for virus inactivation was prevented by the absence of titered hepatitis virus stocks, the lack of an animal model, and the failure to carry out controlled trials. Finally, it was not appreciated that the power of these procedures lay especially in their use in combination. These deficits have now been remedied. To permit quantitation of process efficacy, a regression analysis of the relation between virus dose and incubation period in chimpanzees has been carried out. This has provided a means of estimating virus titer and determining the accuracy of such estimates. The most recent data suggest that betaPL/UV can reduce the titer of hepatitis B virus about 10 million fold (10(-7)). The process efficacy for betaPL/UV followed by the special adsorption procedures used in preparation of a stabilized human serum containing most human serum proteins except for factor VIII, the factor IX complex, fibrinogen, and the lipoproteins was estimated as a 10(8)-fold reduction in virus titer. This degree of virus inactivation should be more than sufficient to sterilize the amounts of hepatitis B virus that could be expected in pooled human plasma that has been screened for hepatitis B surface antigen. Preliminary data also suggest that the betaPL/UV procedure effectively inactivates non-A, non-B hepatitis virus(es).