Contract Development and Manufacturing Organizations (CDMOs) that manufacture large, diverse portfolio of chemical and pharmaceutical substances require pragmatic risk‐based decisions with respect to the safe carry‐over between different chemical entities, as well as for worker protection. Additionally, CDMOs may not have access to primary study data, or data are generally lacking for a specific substance. While pharmaceuticals require the establishment of health‐based exposure limits (HBELs) (e.g., occupational exposure limits OELs and permitted daily exposure PDE limits), the limits for nonhazardous substances could be set in a protective and pragmatic way by using default values, when internally required. Because there is no aligned definition provided by authorities, nor agreed default values for nonhazardous substances, we provide a decision tree in order to help qualified experts (such as qualified toxicologists) to identify the group of nonhazardous substances and to assign default HBEL values for specific routes of exposure. The nonhazardous substances discussed within this publication are part of the following subgroups: (I) inactive pharmaceutical ingredients, (II) pharmaceutical excipients or cosmetic ingredients, (III) substances Generally Recognized as Safe (GRAS), and (IV) food ingredients, additives, and contact materials. The proposed default limit values are 1 mg/m3 for the OEL and 50 mg/day for the PDE oral and intravenous (IV) route. Contract Development and Manufacturing Organizations (CDMOs) work with a large, diverse portfolio of pharmaceutical substances, thus, often need a pragmatic approach to apply risk‐based decisions for patient and worker safety during manufacturing in multipurpose facilities. This work provides guidance on identifying and setting default health‐based exposure limits (HBELs) for defined nonhazardous substances in pharmaceutical manufacturing in line with regulatory guidelines.