Abstract
The current Good Manufacturing Practice (cGMP) and effluent emission (use and disposal) regulations of the U.S. Food and Drug Administration (FDA) and manufacturing effluent discharge and emission regulations of the U.S. Environmental Protection Agency (U.S. EPA) require contained manufacture, use, and disposal of pharmaceuticals with the goal of minimizing the release of pharmaceutical chemicals into the environment. However, debate has recently arisen in several scientific forums over whether these regulations adequately protect human and environmental health from the new pharmaceutical drugs introduced each year into the marketplace and the multitude of existing products, each with many distinct biochemical modes of actions. To address this issue, it is important to understand the relevance of current cGMP regulations and emission regulations that have a direct bearing on the releases of pharmaceutical chemicals into the environment during the manufacture, use, and disposal of active pharmaceutical ingredients (drug substances) and drug products. This knowledge may help us assess the quantity of residues that may be released into the environment. Additionally, the information on physical, chemical, and degradation and sorption properties of the pharmaceutical chemicals may help determine the net residue levels that could persist in the environment to evaluate if such residues have any bearing on human and environmental health. The scientific and regulatory aspects of issues related to the manufacture, use, and disposal of pharmaceutical chemicals are discussed in this article, with special emphasis on potential environmental exposure pathways during the life cycle of an active pharmaceutical ingredient or drug product. The mechanisms of degradation (transformation or depletion) and dilution of pharmaceutical residues that may be released into aquatic or terrestrial environmental compartments are described. Such degradation and dilution of pharmaceutical chemicals in the environment may significantly reduce the residues. It is important to evaluate whether such residue levels have any measurable impact on human and/or environmental health.