Retrospective Evaluation of Cycled Resin in Viral Clearance Studies - A Multiple Company Collaboration - Post ICH Q5A(R2) Review

Abstract

In 2019, the BioPhorum Development Group Viral Clearance Workstream performed a collaborative retrospective analysis to evaluate packed bed chromatographic resin performance after repeated cycling for two commonly used chromatography steps in biopharmaceutical manufacturing: protein A and anion exchange. Key variables evaluated in the assessment included virus type, resin type, number of reuse cycles, and virus challenge.

This paper has been amended to include additional commentary on the ICH Q5A revision adopted in November 2023. In this retrospective analysis of viral clearance data on naïve versus cycled resin, powered by the availability of decades' worth of accumulated industry data, clearance capability was not negatively impacted by resin cycling. This finding is consistent with publications showing that surrogates for viral clearance capabilities could be employed in lieu of testing of viral clearance of cycled resins for protein A and anion exchange chromatography. The rigorous analysis of the retrospective data supports the view that viral clearance studies for cycled protein A and anion exchange resins are not necessary, provided that appropriate cleaning methods are applied during repeated use of chromatography columns. In agreement with this paper, ICH Q5A(R2) acknowledges that used resin studies are not required for Protein A. Used resin evaluation is still required for other chromatography steps; however, with appropriate justification, prior knowledge may be used in place of product-specific studies.