Developing Acceptable Surface Limits for Occupational Exposure to Pharmaceutical Substances

摘要

Acceptable surface limits (ASLs) are developed in order to establish a quantitative measure for the potential risk from exposure by dermal contact. In the Pharmaceuticals industry, ASLs are used for protection against active pharmaceutical ingredients that are known to cause pharmacological or toxicological effects. An ASL can be used, together with appropriate analytical methods and industrial hygiene monitoring, to assess workplaces for potential dermal exposure and to protect the health and safety of individuals who might come in direct contact with contaminated surfaces in the workplace. ASLs are also used to evaluate the adequacy of housekeeping measures and the effectiveness of engineering containment approaches, or to determine whether a chemical is present on surfaces where it is not intended to be (e.g., in lunch rooms or offices, or on the outside surfaces of packaging materials). However, they should not be confused with cleaning limits for the surfaces of manufacturing devices that might come into contact with the drug product, which are set to minimize cross contamination between drug products and to protect end-users (e.g., patients taking drug products) as opposed to workers. A number of parameters must be evaluated in order to accurately develop appropriate and scientifically supportable limits. These include the dose or concentration that will cause the potential effect, the degree of chemical transfer from contaminated surfaces to the skin, and the rate or amount of percutaneous absorption. In practice, this information is usually limited or unavailable. Additionally, there has been very little regulatory guidance on the setting of ASLs. Consequently, in order to calculate an ASL, various assumptions must be made by health and safety professionals regarding how dermal exposures might occur. As quantitative data become available, the ASL can be adjusted accordingly. An overview of the setting of health-based and performance-based ASLs for pharmaceutical substances from animal and human toxicological data is provided.