Bovine sera used in the manufacture of biologicals: current concerns and policies of the U.S. Food and Drug Administration regarding the transmissible spongiform encephalopathies

Abstract

Since 1993, consistent with its statutory responsibility to ensure that regulated products are safe, pure, and free of << extraneous organisms, >> the United States Food and Drug Administration (FDA) has requested that, with certain exceptions, bovine-derived materials from animals born in or residing in countries where bovine spongiform encephalopathy has occurred, should not be used to manufacture products intended for humans. FDA's Center for Biologics Evaluation and Research (CBER) has specifically recommended that serum used to produce biologicals be obtained from sources << certified to be free from contaminants and adventitious agents, such as the agent responsible for the production of Bovine Spongiform Encephalopathy. >> The United States Department of Agriculture (USDA) has prohibited importation of such serum for use in products. FDA staff are aware that bovine blood, including foetal blood, and placental tissues and fluids that might contaminate foetal serum have not been found to contain the infectious agent of BSE, and that those tissues are considered by most authorities to have little risk for transmitting disease to humans or animals. However, studies of BSE have been limited in size and sensitivity, and several experimental studies of scrapie and CJD in rodents found their blood to be infectious. In addition, a recent unpublished study of BSE (requiring confirmation) reported finding infectivity in the bone marrow of cattle. Possible transmission of BSE from cows to calves, although unlikely to constitute a major mode for maintaining the BSE outbreak, has also not been rigorously ruled out. Considering the special nature of biological products, especially of vaccines intended for widespread use in children, it seems prudent for U.S. regulatory authorities to continue current conservative policies that discourage or prohibit the use of bovine serum from countries with BSE.