title: Validation of removal of human retroviruses.
abstract: Validation of virus removal during product manufacture is one of several techniques which can be used to help establish product safety. The usefulness of the validation technique will be illustrated for the manufacture of immunoglobulins by the Cohn-Oncley ethanol fractionation procedure in which the partitioning and inactivation of HIV were studied, and for the manufacture of Factor VIII. In the case of Factor VIII which was contaminated with HIV and transmitted infection to product recipients, several manufacturers explored means of eliminating infectious virus by using a validation procedure involving a scaled-down manufacturing process and the spiking of individual steps to determine the extent of removal from the product and the inactivation of virus during manufacture. Assays for virus remaining after each step were performed in tissue culture. Some products were also tested in chimpanzees. Results of tissue culture assays could be correlated with safety testing in animals, and also with subsequent retrospective analysis of actual product use in patients. Correlation was good, suggesting that process validation is useful. Current use of virus validation to assess virus removal from products made from continuous cell lines such as human hybridomas which could potentially contain viruses infectious for humans, as well as some limitations of these validation techniques are also discussed.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, MD.
authors.forename: C J
authors.initials: CJ
authors.lastname: Marcus-Sekura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D001688:Biological Products / Q000302:isolation & purification*; D002460:Cell Line; D004340:Drug Contamination / Q000517:prevention & control; D005169:Factor VIII / Q000302:isolation & purification; D006678:HIV / Q000302:isolation & purification; D006801:Humans; D007136:Immunoglobulins / Q000302:isolation & purification; D012190:Retroviridae / Q000302:isolation & purification*; D012449:Safety
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D007136:Immunoglobulins; D005169:Factor VIII