A Biosafety Toolbox for Manufacturing with Single-Use Systems.

Abstract

As markets for recombinant biologicals constantly grow, the risks related to the biohazardous materials used are not yet always understood and assessed systematically. Thus, there is a strong need to systematically assess technical solutions in the good manufacturing practice (GMP) area and best practices for all steps in biotechnological production using biohazardous materials up to biological safety level 2 (BSL2). Especially viral vectors, as virus-based vaccines are coming to market as novel therapies, asking for different safety requirements. As single-use solutions (SUSs) are widely used in clinical and production scale in upstream and downstream processing until final fill operations, new practices must be developed with a different approach to enable production under BSL2. Production of biologics that are produced in the BSL2 area regime using SUSs must be reviewed under different aspects in terms of safety for the product and staff equally and probable contamination of the environment. SUSs for this new purpose must be differently handled with care from goods entry until final discard of products post usage. The production starting at fabrication of the SUS items itself might require modifications. The design of SUS items for the BSL2 purpose must be tested already in a different way in production to fulfill the higher safety level regimes to protect the product and operators. In this paper, we give examples for consideration of how to unpack and store such SUS consumables and which conditions in the facility are favorable in combination with proper staff training. Examples of suitable components and existing SUS equipments for the upstream and downstream processing of such products, to give operators, suite and plant managers, A + E with planners, and people in regulatory departments the needed information to enable the safe and regulatory aligned production of such biologic therapies.