Validation of purification procedures for removing and/or inactivating viruses in biologicals: points to consider.

: Viruses represent a main concern as a potential risk associated with the use of both classical biologicals and new biotechnological products. The objective of validation is to estimate quantitatively the overall level of virus clearance obtained during the various stages of purification and viral inactivation procedures. The design of a validation procedure should take into account the amount of contaminating virus in the source material, the minimum clearance factor to be attained for at least one of the stages and the minimum overall clearance factor. A major issue in performing a validation assay is in determining what viruses should be used. In addition to the inclusion of relevant viruses in the assessment, the validation should include a collection of model viruses possessing a range of biophysical and structural features and displaying a significant resistance to physical and/or chemical agents. Despite the apparent freedom from any infectious agents of source materials, such as plasma or cell lines, validation of the purification and/or inactivation procedures plays an essential and important role in establishing the safety of biologicals.