Prior to entering clinical trials viral clearance studies are mandated for commercial launch of biopharmaceuticals. These studies are a key component of risk mitigation to reduce the potential for iatrogenic transmission of pathogenic viruses. In this publication, we review regulatory guidance and practical strategies for designing viral clearance studies. Essential elements of a developmental phase-appropriate viral clearance package are detailed. These include scale-down model qualification, virus spike experiments and validation (clearance evaluation) of manufacturing process steps. Also shared are heuristics and learnings from available data. Developments in this area including generic validation strategies, multiviral spiking strategies and use of newer model viruses for nonconventional substrates are also described. This review provides a framework for a comprehensive viral validation package for regulatory submissions.
Viral clearance; Risk assessment; Relevant virus; Specific model virus; Process robustness; Nonspecific model virus