RNA therapeutics-An evaluation of potential occupational health hazards and a strategy to establish occupational exposure limits (OELs).

Abstract

RNA therapeutics represent a rapidly expanding and innovative group of pharmaceuticals. These new modalities necessitate the establishment of Occupational Exposure Limits (OELs) to ensure safe occupational handling. While there is an established methodology for setting OELs for small molecule therapeutics, this methodology is not readily applicable to large molecule RNA therapeutics that deserve additional considerations in their safety assessment, particularly for aspects related to their unique modes of action. This research, which involves an extensive review of the data available for RNA therapeutics to derive substance-specific OELs and to propose a strategy for low-characterized RNA therapeutics, fills this crucial gap. It is recommended to apply an activity correction factor (ACF) in the OEL formula for large molecules, as representative of the "α" in the OEL formula for small molecules, considering differences in route of administration, critical effects, mechanism of action, and the RNA delivery platform. Additionally, it is proposed to consider lower OEL values for mRNA vaccines as compared to other RNA therapeutics. Finally, it is suggested that the exposure assessment experience that has already been acquired when handling therapeutic proteins can also be used to define containment strategies for RNA therapeutics.