Here at Affygility Solutions, we often get asked the question, “I’m being told that I need to find out the OELs for all my active pharmaceutical ingredients, but I don’t even know why I need them. Can you help?”

What is an Occupational Exposure Limit (OEL)?

So let me explain: Occupational exposure limits (OELs) are defined as the time-weighted average concentration of a contaminant, measured in the employee’s breathing zone, that is considered to be safe for the majority of healthy workers, for an eight-hour work shift and a forty-hour work week, and entire working lifetime.

OELs are health-based values that are established by expert toxicologists reviewing existing published, peer-reviewed literature, and scientific databases. In addition, for new chemical entities (NCEs), it may be necessary to review pre-clinical and clinical data to determine the OEL. Based on the currently available information, the expert toxicologists formulate a conclusion on the level of exposure that the average worker can experience without adverse health effects.

Since OELs are based solely on health factors, unlike regulatory limits such as permissible exposure limits, there is no consideration to the economic impact or the technical barriers of containing a compound to below that airborne concentration. In addition, in regards to OELs, it is important to remember the following points:

1. OELs are generally not considered to be legal limits as defined by the United States Occupational Safety and Health Administration (OSHA) or other occupational safety regulatory agencies;
2. OELs are not fine lines between safe and dangerous conditions; and
3. The OEL for a specific compound may change.

Why are Occupational Exposure Limits important?

OELs are important because it defines a target for the unit operation’s containment capabilities and strategies. In addition to preventing occupational illness, effective containment is critical for the prevent cross-product contamination. For compounds with relatively high OELs (greater than 100 ug/m³), containment can be achieved with a modest amount of engineering and administrative controls. For compounds with very low OELs (less than 1 ug/m³), it will be necessary to implement more elaborate controls. Many factors are involved in the selection of engineering controls (scale, duration of the activity, physical form of the material, energy imparted on the process, etc.) and it is beyond the scope of this article to discuss the entire process. At this point I should mention, that the use of personal protective equipment (PPE), such as respirators, should not be the primary means of controlling exposure to below the OEL. PPE should only be used either as a secondary means of protection, or as a temporary means of protection while engineering controls are being implemented.

Engineering Controls must be Validated

Once engineering controls and other containment strategies have been implemented, it is critical to validate the containment capabilities. This is typically done by a qualified industrial hygienist performing containment validation monitoring, which is a form of both operator exposure monitoring and area monitoring. While it is preferred to perform compound-specific air monitoring; often, many drug compounds may not have validated industrial hygiene air sampling and analytical methods. In this case, it may be necessary to use surrogate compounds such as naproxen sodium, lactose, or mannitol to determine in the effectiveness of the containment equipment. If the results of the containment validation monitoring indicate that airborne concentrations are above the OEL, it may be necessary to improve the existing controls or implement additional controls.

Summary

The establishment of occupational exposure limits are critical for protecting the health of workers in the pharmaceutical industry. OELs assist in defining the containment performance target of the engineering controls used in a unit operation. Once these controls have been installed, the controls must be validated, using either compound-specific or surrogate air monitoring. The importance of having an OEL is not just having the number, but it is ensuring that your containment is effective at preventing occupational illness and reducing the probability of having cross-product contamination. Since the advent of the EMA's requirement for health based exposure limits in shared facilities and the need for PDE reports, there has also been a greater interest in establishing OELs for active pharmaceutical ingredients.

If you have any questions, please feel free to reach out to the occupational health and safety experts at Affygility Solutions.

Published October 11, 2017 / Updated June 18, 2021

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