title: Analysis of viral clearance unit operations for monoclonal antibodies.
abstract: Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.
authors.affiliation: Office of Biotechnology Products, CDER/FDA, 10903 New Hampshire Ave., Silver Spring, Maryland 20903, USA. george.miesegaes@fda.hhs.gov
authors.forename: George
authors.initials: G
authors.lastname: Miesegaes
authors.forename: Scott
authors.initials: S
authors.lastname: Lute
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
mesh_terms: D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D018929:Cell Culture Techniques / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D014780:Viruses / Q000737:chemistry* / Q000302:isolation & purification*
chemical_list: D000911:Antibodies, Monoclonal