Performance-based exposure control limits for pharmaceutical active ingredients.

Abstract

For many years pharmaceutical companies have established employee exposure limits for the active ingredients used in their products. Historically these limits were derived using traditional risk assessment methods. Because the trend in the pharmaceutical industry is to identify and develop more selective drugs of increasing potency, and because of the difficulty in identifying no-effect levels for certain drugs, a new performance-based approach for setting limits was developed. This method involves assigning materials into one of five hazard categories according to their inherent toxicological and pharmacological properties. The criteria used to assign compounds into performance-based exposure control limit (PB-ECL) categories focus on the degree to which exposure impacts human health. These assignments dictate the level of containment required to assure employee safety that is achieved through the use of engineering controls and safe handling practices. Several matrices were developed to specify general design concepts and controls for unit operations in laboratory and manufacturing operations. Containment options range from conventional handling practices for low potency (PB-ECL Category 1) materials, to technologically advanced systems that result in essentially no open handling for potent or toxic (PB-ECL Category 3) materials, to state-of-the-art facilities employing closed processes and use of robotics for extremely potent (PB-ECL Category 5) materials.