Proceedings of the 2019 Viral Clearance Symposium, Session 4: Viral Clearance Strategy and Process Understanding

Abstract

This article describes a summary of discussions and outcomes from the 2019 Viral Clearance Symposium Session 4 on the utilization of knowledge, both from within and external to a given organization (e.g., across the interdisciplinary space), that supports viral clearance strategy and process understanding, including engagement with Health Authorities in the development and implementation. Several significant areas were identified for prioritization in an ICHQ5A update including application of next-generation sequencing (NGS) and replacement of in vivo tests, resin reuse, and use of a parvovirus as a single model virus for virus filtration. Specific opportunities were identified based on case studies for application of prior knowledge to support risk assessments, to guide viral clearance study designs, and to support viral clearance claims based on a limited number of confirmatory runs. One discussion focused specifically on how to apply best practices and prior knowledge to an assessment of the potential impact of resin reuse on viral clearance. Prior experience showed a trend toward larger log reduction values (LRVs) with reused protein A resin. For other resins, differences in LRV (>1.0) between new and reused resins were mainly found when validation was performed in independent studies, not side by side. Another example of applying prior knowledge was an assessment of potential variability and worst-case retrovirus-like particle (RVLP) levels in unprocessed bulk presented by Paul-Ehrlich-Institut. The opportunity to utilize noninfectious surrogates for viruses (such as RVLPs or parvovirus-like particles) in screening experiments to determine the impact of process parameters on viral clearance, and the associated current limitations owing to analytics, was also reviewed.