Viral Clearance in Biomanufacturing
Viral contamination is an inherent risk during the manufacture of therapeutic products such as antibodies, vaccines, and plasma derivates. Whether introduced endogenously from raw materials or exogenously through manufacturing operations, unmitigated viral contaminations have led to serious health implications and plant shut downs. International regulatory agencies therefore require sponsoring companies to validate the “viral clearance efficacy” of their individual downstream purification process steps prior to clinical trials or commercial approval.
Viral clearance validation is assessed through small scale “spiking studies” whereby model mammalian virus (ex. Minute Virus of Mice) is introduced into in-process material which is then processed through a purification technique (ex. chromatography, nanofiltration, low pH, etc.). Viral quantity pre/post processing is determined through an infectivity (ex. TCID50) or qPCR assay and Log Reduction Value is calculated. These studies require specialized Biological Safety Level laboratories (BSL) and experienced personnel.
- EMEA, Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products, 2008 – EMEA/CHMP/BWP/398498/2005
- ICH, Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin, Topic Q5A (R1), 1997
- EMEA, Overview of Comments Received on Draft Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products, 2008 – EMEA/CHMP/BWP/67410/2007
- International Conference on Harmonisation; guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin; availability – FDA, Notice, Fed Regist, 63(185): pp51,074-51,084, 1998
- FDA Center for Biologics Evaluation and Research, Points to consider in the manufacture and testing of monoclonal antibody products for human use, J Immunother 20(3): pp214-243, 1997
- Committee for Proprietary Medicinal Products (CPMP). Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses. CPMP/BWP/268/95;1996 Feb