Viral safety issues for biological products

Approaches to viral safety issues for biological products have evolved during the past 50+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 deriv atives introduced the that purification and treatment with physical physical and chemical agents could greatly reduce the risk of viral contamination of human and immunoglobulin products. But the limitations of such approaches became clear for ther molabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and and HIV -1 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 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 viruses, screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viralv clearance for safety of biotechnology products. 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. Screening tests for viral contamination in raw materials have not proven practical by themselves to prevent contamination of cell cultures, but they can be made effective by coupling wit treatment using physical or chemical agents to further reduce the hypothetical viral viral loads present in cell culture raw materials. Recent advances in polymerase chain reaction (PCR) technology have allowed preharvest 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.

Keywords:

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