Designing Successful Viral Clearance Studies

By Kathryn Martin Remington, Ph.D., and Kate Smith

Ensuring that biopharmaceuticals are free from the presence of adventitious viruses is critical to the safety of these products. Viruses can be as simple as a genome surrounded by a protein shell, yet a single infectious virion can replicate in susceptible cells and lead to widespread contamination. Implementation of a viral safety strategy involves a multi-pronged, complementary approach. This includes selecting and testing cell lines and critical raw materials to ensure the absence of adventitious viruses. For products that are directly derived from human or animal plasma or other tissues, testing of those raw materials is especially critical.

Despite careful testing of starting materials and in-process intermediates, there is still a risk that a virus could enter the manufacturing process undetected. Steps in the manufacturing process that might inactivate or remove viruses act as a final safety net to ensure that the final product is safe from a viral contaminant. The capacity of the manufacturing process to remove or inactivate enveloped and nonenveloped viruses is assessed in viral clearance studies. These studies, which we will go into more detail throughout this paper, involve scaling down individual process steps, and for each step, spiking virus into the specific process intermediate, performing the process step, and measuring the virus remaining after the process step.