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Published on: February 23, 2020
Disease area and mode of action as criteria to assign a default occupational exposure limit
Milica Glogovac1, Caylee Paulson1, Amy Lambert2
1Novartis Pharma AG, Novartis Business Services, Postfach, CH-4002, Basel, Switzerland.
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.
Insights
A default occupational exposure limit (OEL) of 10 μg/m³ is a safe inhalation exposure level for new drug candidates lacking toxicological data. This finding aids early-stage risk assessment for laboratory personnel.
Area of Science:
- Pharmaceutical Sciences
- Occupational Health
- Toxicology
Background:
- Early drug development lacks toxicological data for new small molecule drug candidates (DCs).
- Calculating occupational exposure limits (OELs) for these DCs is impossible without toxicological data.
- An OEL is crucial for determining protective measures for laboratory researchers and technicians.
Purpose of the Study:
- To evaluate the applicability of a default OEL for data-poor drug candidates.
- To assess if disease area and mode of action can inform OEL assignment.
- To provide guidance for early-stage risk assessment of small molecule DCs.
Main Methods:
- Evaluated 860 drug substances (DS) with pre-calculated OELs.
- Grouped DSs by disease area (DA) and mode of action (MoA).
- Analyzed the distribution of OELs across different DAs and MoAs.
Main Results:
- 72% of evaluated DSs had an OEL ≥10 μg/m³, while 28% had an OEL <10 μg/m³.
- The default OEL of 10 μg/m³ was confirmed as a reasonably safe exposure limit for data-poor small molecule DCs.
- Certain DAs and MoAs were identified as potential criteria for predicting DCs requiring a default OEL <10 μg/m³.
Conclusions:
- The default OEL of 10 μg/m³ is a reliable safety benchmark for early-stage drug candidates.
- Integrating DA and MoA into risk assessment strategies can help identify high-hazard DCs early.
- This approach supports robust occupational health and safety in drug research and development.
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