Viral contamination is an inherent risk during the manufacture of therapeutic products such as antibodies, vaccines, viral vectors, and plasma derivates. Whether introduced endogenously from raw materials or exogenously through manufacturing operations, unmitigated viral contaminations can lead to serious health implications and plant shutdowns. Therefore, international regulatory agencies require sponsoring companies to validate the “viral clearance efficacy” of their individual downstream purification process steps before clinical trials or commercial approval .
Viral clearance validation is assessed through small-scale “spiking studies,” where model mammalian viruses (e.g., Minute Virus of Mice [MVM], or Xenotropic Murine Leukemia Virus [XMuLV]) are introduced into in-process material that is then processed through a purification technique (e.g., chromatography, nanofiltration, and low pH). Viral quantity pre/post-processing is determined through an infectivity (e.g., TCID50) or qPCR assay and the log reduction value (LRV) is calculated.
Spiking studies require specialized contract research organizations (CRO’s) and trained personnel resulting in high costs and complex logistics. These hurdles deter companies from analyzing viral clearance during the years of small-scale process development. Instead, companies spend considerable resources optimizing manufacturing processes before gaining any knowledge of their viral clearance efficacy. Unfortunately, this increases the risk of validation failure, forcing companies to invest additional time and money redeveloping process steps, which in turn, could postpone regulatory approvals and delay patients’ timely access to therapies.
To help de-risk your downstream purification process and assess viral clearance early in process development, Cygnus provides a unique solution that enables viral clearance prediction early in downstream purification development. Now, through the use of BSL-1 compatible viral clearance kits, you can easily and economically quantify viral clearance for downstream process steps in your own lab, on your own timeline.
 Q5A Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human of Animal Origin, ICH, 1997 (Adopted as a guidance document and published in Federal Register September 1998).