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).
Cygnus Technologies offers the MockV™ MVM Kit, as a BSL-1 compatible viral clearance prediction tool. This kit utilizes non-infectious surrogates to perform quantitative clearance analysis, enabling benchtop scientists to easily and economically quantify viral clearance in industrial processes gaining actionable insights into your process early in downstream purification development.
Cygnus’ MockV® RVLP Kit provides a highly purified and concentrated BSL-1 compatible stock solution of non-infectious Retrovirus-like Particles (RVLP) along with the necessary reagents for accurate and reliable RVLP quantification. RVLP is an actual non-infectious retrovirus-like contaminant generated during CHO production. In the early 1990’s, global regulatory agencies such as the FDA realized the prevalence of this particle and became concerned about the retroviral safety of CHO-derived biopharmaceuticals. Since then, the biopharmaceutical industry has relied on CRO’s to propagate XMuLV as a model retrovirus to demonstrate effective clearance. With the availability of the MockV® RVLP Kit, biopharmaceutical companies can now independently assess the removal of the original retroviral particle of regulatory concern, derived directly from CHO cells.
What BioProcess International Magazine readers say about this study:
“This paper highlighted a novel way to predict viral clearance. For 20+years, our industry has relied on expensive and logistically challenging studies led by contract organizations. The technique that the authors
describe will be a paradigm shift for process developers.”
“This publication is especially relevant for addressing today’s challenges in gene therapy development, both from a manufacturability perspective and in terms of ensuring a safe and efficacious product.”
“This article will be fundamental for developing manufacturing processes and optimizing purification of gene therapy products with a parallel focus on