Analysis of viral clearance unit operations for monoclonal antibodies.
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.
Miesegaes
George
G
Office of Biotechnology Products, CDER/FDA, 10903 New Hampshire Ave., Silver Spring, Maryland 20903, USA. george.miesegaes@fda.hhs.gov
Lute
Scott
S
Brorson
Kurt
K
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*
D000911:Antibodies, Monoclonal