Proceedings of 2017 Viral Clearance Symposium Session 5: Facility Risk Mitigation

Abstract

The discussion on the facility risk mitigation was included in the 2017 viral clearance symposium for the first time. There were a few topics discussed in this session, including sanitization / cleaning against viruses, viral segregation as well as definition of a functionally closed system. Virus inactivation by disinfectants is critical for the biotechnology industry. The efficacy can be different, depending whether applied to surfaces, in solutions or in the gas phases, as well as the respective disinfectants, i.e., peracetic acid - hydrogen peroxide-based, hypochlorite-based or glutaraldehyde-based. Most equipment used in biotech industry can be cleaned or sanitized by alkaline solutions. Many of these methods were studied with regard to their virus reduction potential and were defined considering alkaline concentration, time and temperature. Virus clearance may potentially be compromised if cross contamination or carryover happens, from an early step with potentially a higher level of virus to a step later in the purification process, i.e., after virus removal or inactivation. Critical potential carryover (Vcpc) is defined as the volume of carryover that will significantly affect the overall virus clearance of a purification process. Based on the evaluation of critical potential carryover, mitigation actions can be introduced to avoid such carryover. Appropriate segregation within manufacturing facilities is required by regulators and utilized by manufacturers to ensure that the final product has appropriate safety margins. However, there is a lack of consensus around basic definitions and approaches related to facility segregation. To address this gap, the member companies of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) have begun a project with the goal of developing a definition for a "functionally closed" manufacturing system.