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
Due to the high costs and logistics associated with viral clearance studies, most companies delay assessments until just prior to regulatory validation. Thus, considerable up-front resources are spent developing and optimizing a downstream purification process in which little is known in terms of viral clearance efficacy. This increases the risk of validation failure, forcing companies to invest additional time and money redeveloping process steps.
Analytic kits are ubiquitously used throughout small scale process development to determine the removal of other critical impurities such as Host Cell Proteins, DNA, and Endotoxin. These kits are important low cost tools that help scientists optimize process steps before validation and manufacturing scale-up. We, at MockV Solutions, seek to establish a line of low cost viral clearance prediction kits which will introduce a “Quality by Design” approach to viral clearance during small scale process development and optimization.
Our approach is through the use of Mock Virus Particles (MVPs). MVPs are multiprotein structures that mimic the physicochemical characteristics, organization and conformation of native infectious viruses but are themselves non-infectious. Our kits will feature a highly purified and concentrated stock solution of MVP for use as a “spiking agent” and reagents for conducting a sensitive quantification assay. To perform a VLP spiking study, a scientist would:
- Add MVP stock solution to the in-process material
- Process the “spiked” material through a purification technique
- Analyze MVP quantity pre/post processing to determine Log Reduction Value
MockV Solutions is building a library of MVP Kits that will address the various needs of benchtop scientists. Each BSL-1 compatible kit will contain the necessary reagents to conduct Mock Virus Particle spiking experiments including: a concentrated and purified stock solution of MVP and quantification reagents. To learn more about our kits in development, click on the images to the right. To inquire about or request additional kits that may address the needs of your industry, please contact us.