Transmissible Spongiform Encephalopathy and Medicinal Products in the United States and Europe

Abstract

Transmissible spongiform encephalopathy (TSE) is an inclusive term for a group of slowly progressing, neurodegenerative diseases with long incubation periods. Design and validation of manufacturing processes that eliminate TSE agents is difficult because of TSE resistance to standard chemical and physical measures and the lack of quick, reliable diagnostic assays. Thus, preventive measures have been put into place by regulatory authorities. Bovine spongiform encephalopathy (BSE), the cause of “mad cow disease,” is of particular concern since it is believed to cause Creutzfeld-Jakob disease in humans. Many medicinal products contain or come in contact with substances of bovine origin during manufacture. As a consequence, regulations and guidances have been established in the United States and Europe for bovine-derived materials used in manufacturing medicinal products. Manufacturers must assess active substances, excipients, raw materials, production reagents, and materials coming into direct contact with manufacturing equipment or product containers. United States and European regulatory authorities have used different approaches toward documentation required for bovine materials used in the production of medicinal products. The relevant documentation must be included in the investigational or marketing application.