Theory and practice of conventional adventitious virus testing.

CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) For decades conventional tests in cell cultures and in laboratory animals have served as standard methods for broad-spectrum screening for adventitious viruses. New virus detection methods based on molecular biology have broadened and improved our knowledge about potential contaminating viruses and about the suitability of the conventional test methods. This paper summarizes and discusses practical aspects of conventional test schemes, such as detectability of various viruses, questionable or false-positive results, animal numbers needed, time and cost of testing, and applicability for rapidly changing starting materials. Strategies to improve the virus safety of biological medicinal products are proposed. The strategies should be based upon a flexible application of existing and new methods along with a scientifically based risk assessment. However, testing alone does not guarantee the absence of adventitious agents and must be accompanied by virus removing or virus inactivating process steps for critical starting materials, raw materials, and for the drug product.