Broadening our expectations for viral safety risk mitigation.

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) The production of biotechnology products using mammalian cell lines offers an inherent risk of viral contamination because of the scale of the process and the complexity of the materials employed. The testing of production cell lines, raw materials, and test execution at appropriate stages of production all combined with viral inactivation or removal strategies ensures that an infectious agent is absent from the purified final product. Perhaps because of these efforts, biotechnology products have not been linked to a negative clinical consequence. However, manufacturing viral contaminations still do occur and may have a great potential negative impact to our patients by disrupting the drug product supply chain. In this paper, additional end-to-end complementary viral safety program considerations are suggested beyond the traditional viral testing and inactivation/removal strategies. These additional points of consideration should be thought of as augmenting the above approaches to further provide a reasonable measure of mitigating the risk of viral contaminations within the biopharmaceutical manufacturing facility. The scope of this paper is on biologics produced in mammalian cells with an emphasis on viral contaminations involving Chinese hamster ovary cell production, although for the examples given as lessons learned with previous industry contaminations, vaccine production issues have been included as a general reference.