Predicting Viral Clearance In Downstream Process Development

By David Cetlin, senior director of research and development, Cygnus Technologies

Viral contamination is an inherent risk during biopharmaceutical manufacturing. Whether introduced endogenously from cell banks or exogenously during manufacturing, unmitigated\viral contaminations have led to serious health implications, including transmission of influenza, human immunodeficiency virus (HIV), hepatitis, herpes, measles, and poliomyelitis. International regulatory agencies, therefore, require biopharmaceutical companies to validate the viral clearance efficacy of their manufacturing processes before clinical trials and commercial approvals.

Currently, validation is performed through small-scale spiking studies, whereby specific model mammalian viruses (e.g., minute virus of mice, MVM) are introduced artificially into biopharmaceutical material and cleared (removed or inactivated) by a subsequent purification technique. Spiking studies require specialized biological safety level (BSL) laboratories and sufficiently trained personnel, resulting in costs that can soar over $US100,000. Such hurdles deter companies from analyzing viral clearance during small-scale process development. Instead, sponsors delay assessments and spend considerable resources up front optimizing purification process steps without knowing their viralclearance efficacy. However, that increases the  risk of validation failure and can force companies to invest additional time and money redeveloping process steps when failures occur.

In this paper we review a the use of mock virus particle (MVP) kits to support a quality-by-design (QbD) approach. Scientists can optimize purification steps and determine with confidence whether process steps and parameters are effective before investing significant resources in regulatory supporting validation studies using live virus.

BioProcess International 19(5)si May 2021