Limiting Active Pharmaceutical Ingredients in Manufacturing Effluent

<p>The improved precision and accuracy of analytical methods for trace organic chemicals, which include pharmaceutical products and many other types of consumer products, has led to concerns about potential exposure to humans, animals and aquatic life. Humans and companion animals, for example, could potentially be exposed to these chemicals via drinking water and aquatic biota could be exposed in surface waters.</p><p><br></p><p>It should be noted that like any chemical product following disposal and excretion, low concentrations of pharmaceutical compounds are expected to be detectable in water. Equilibrium chemistry dictates that all chemicals used will be distributed in the environment. This means that even compounds that are highly degradable may be detected in the environment in very small concentrations given adequate analytical methods. Therefore, it is important to evaluate the risks associated with these concentrations.&nbsp;Studies have shown that for medicines found in surface waters, the detected concentrations of pharmaceutical products are far below levels that may affect human health.</p><p><br></p><p>While the major route for <a href="https://www.jinzongmachinery.com/intermediate-manufacturing-plant" rel="noopener noreferrer" target="_blank"><strong>active pharmaceutical ingredients (APIs) manufacturing plant</strong></a> to reach water is via excretion from patients following prescribed usage, there is widespread concern for contamination from manufacturing effluents. Therefore, it is important to reduce wastewater discharges of APIs to levels below thresholds of concern. Unfortunately, for many older, previously approved pharmaceuticals on the market, little or no environmental fate and effects data are available. Additionally, during the research and development of APIs, chronic aquatic data are usually not developed until the drug reaches Phase II or III human clinical trials. Chronic studies are generally performed on fish, daphnia and algae, per the EU and U.S. guidelines for environmental risk assessments of pharmaceuticals.However, these studies may take up to two years to complete. Therefore, a process must be in place to ensure wastewater concentrations do not exceed potentially toxic thresholds of APIs prior to a pharmaceutical going to market, i.e., during research and process scale-up activities. Once production of larger quantities is possible, chronic toxicity studies are initiated and chronic aquatic data are derived.</p><p><br></p><p>&nbsp;Previous research has shown that acute toxicity data may be leveraged as screening tools when chronic data are unavailable.Therefore, preliminary predicted-no-effect concentrations (PNECs) can be calculated using appropriate assessment factors (AFs) and acute aquatic toxicity endpoints. AFs are intended to account for uncertainty due to inter-species, intra-species and lab-to-field variation. Once established, chronic data can be used, which require less stringent AFs.Special classes of compounds based on their intended mode of action and/or potency may trigger the need for more stringent AFs (e.g., female sex hormones).</p><p><br></p><p>Another important consideration is potential contamination of downstream potable water intakes. Acceptable daily exposure (ADE) values are derived using data from preclinical and clinical studies conducted to evaluate the safety and efficacy of new drugs for patients. These limits are also used to support cleaning validation programs to prevent cross-contamination in multi-product manufacturing facilities and to establish safe levels of exposure for workers handling <a href="https://www.jinzongmachinery.com/pharmaceutical-processing-machine" rel="noopener noreferrer" target="_blank"><strong>APIs</strong></a>.The ADE can also be applied to establish safe levels for humans following potential exposure via the environment.</p><p><br></p>