Viral safety issues for biological products

Background and Aim : Approaches to viral safety issues for biological products have evolved during the past ۵۰+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin productsMethods : But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-۱ to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contam- ination due to human viruses and purification technologies to physically remove and inactivate adventitious and endog- enous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety.Results : Recent advances in polymerase chain reaction (PCR) technology have allowed preharvest testing for specific viral agents to reduce the risk of cell culture contamination by specific viruses in the harvest material. Examples of each of these stages in the evolution of virus detection methods are described and assessed in this paper.Conclusion : These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has occasionally occurred.

کلیدواژه ها:

Viral safety ، In vivo virus screening ، In vitro virus screening ، Adventitious viral agents ، Viral clearance ، Viral inactivation ، PCR testing ، Biological products