Disease area and mode of action as criteria to asssign a default occupational exposure limit.

Abstract

In the early stages of drug research and development, there are only a few or no toxicological data available for newly synthesized small molecule drug candidates (DC). Calculation of the DC s occupational exposure limit (OEL) without toxicological data is not possible. Nevertheless, an OEL is needed to indicate the level of protection required to minimize risks for laboratory researchers and technicians. For this reason, simplified guidance is required to predict possible health hazards of DCs and their corresponding safe inhalation exposure levels. Here, we evaluated 860 drug substances (DS) with OELs calculated by Novartis and grouped the DSs by disease area (DA) and then their mode of action (MoA). 28% of the evaluated DSs (n=242) had an OEL <10 μg/m3 and 72% (n=618) had an OEL ≥10 μg/m3. Our evaluation confirms that in the absence of any compound-specific data, the default OEL of 10 μg/m3 is a reasonably safe exposure limit for small molecule DCs. Furthermore, our analysis suggests certain DAs and MoAs as valid criteria that may be integrated into a company s specific strategy for the assessment of data-poor compounds in order to identify DCs in an early stage of their development which require a default OEL <10 μg/m3.