Implementation of virus filtration unit operations and evaluation of viral clearance under challenging process conditions

Virus retentive filtration (VRF) has been a requirement in mammalian derived biologics purification for decades. As a part of a comprehensive viral safety platform, viral clearance using VRFs has been relied upon to remove both large and small viruses (>20nm) using a well-defined size-exclusion based mechanism. These VRF processes are validated for virus removal capability in viral clearance studies using both relevant and model viruses. While most studies using typical process parameters meet or exceed the viral clearance requirement set by the ICH Q5A, there are specific process conditions that impact viral clearance capability on many filters used in commercial manufacturing processes. These adverse process conditions include effects from process pause or low-pressure filtration and low pH (pH < 6) with high conductivity (>15mS/cm) feed streams. In an attempt to demonstrate these effects using the Sartorius Virosart HF filter, viral clearance studies were carried out that were designed to push virus filter validation to its limits. To do so, two monoclonal antibody feed streams were evaluated using several different pH and pressure conditions. After discussing the results of these viral clearance studies, a thorough evaluation of the use of gamma irradiated single use transfersets and filter assemblies such as the Sartorius MaxiCap MR system will be presented for commercial scale processing.