An updated analysis of viral clearance unit operations for biotechnology manufacturing

Abstract

Viral contamination is a potential risk of using biotechnology products derived from mammalian cell lines. Therefore, to provide assurance of the safety of these products regarding potential viral contamination, regulatory authorities require viral clearance studies assessing the ability of the purification process to clear endogenous and exogenous viruses. A viral clearance database containing viral clearance study data from FDA submissions was initiated in 2008, and an initial analysis of that database was published in 2010. Since 2010, the database has been updated with additional biological license application records through January 31, 2021. Here, we provide an analysis of the updated database incorporating newer manufacturing technologies as well as trends in process design for monoclonal antibody and antibody related products. The updated analyses demonstrate that newer technologies e.g., second generation small virus filters, offer viral clearance performance either comparable to or more robust than the traditional unit operations or technologies. Overall, the viral clearance database provides confirmation through real-world data that the unit operations relied upon for decades continue to provide robust and effective removal of viral contaminants during biotechnology manufacturing, as the technologies associated with these unit operations continue to improve.

Keywords

• Viral clearance
• Low pH inactivation
• Virus retentive filtration
• Chromatography viral clearance
• Pharmaceutical viral clearance
• Retrovirus-like particle clearance