Viral Clearance

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 [1].

Viral clearance validation is assessed through small-scale “spiking studies,” where model mammalian viruses (e.g., minute virus of mice [MVM]) 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. These studies require specialized Biological Safety Level (BSL) laboratories and experienced personnel, resulting in costs that can soar well over US$100,000. These hurdles deter many companies from analyzing viral clearance during the years of small-scale process development that lead to validation. Instead, such companies spend considerable resources optimizing their manufacturing processes before gaining knowledge of viral clearance efficacy. Unfortunately, that increases the risk of validation failure, forcing biomanufacturers to invest additional time and money redeveloping some process steps—which can, in turn, postpone regulatory approval.

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.

[1] 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).

Find a Solution

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.


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
viral safety.”