residualsolvent

Residual solvents are organic volatile chemicals used in the manufacturing of drugs, excipients, and drug products. They are considered process impurities. Their presence in pharmaceutical products is a concern due to potential toxicity. Regulatory agencies like the U.S. Food and Drug Administration (FDA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have established guidelines to limit the levels of residual solvents in drug substances and products.

These guidelines, such as ICH Q3C, classify solvents into three categories based on their toxicity. Class 1 solvents are known or strongly suspected human carcinogens and should not be present in pharmaceutical products. Class 2 solvents have inherent toxicity and should be limited. Class 3 solvents have low toxic potential and are generally permitted in pharmaceutical products at levels up to 50 mg per day.

The analysis of residual solvents is typically performed using gas chromatography (GC). This analytical technique is sensitive and specific for volatile organic compounds. Manufacturers must demonstrate that their products comply with the established limits for residual solvents to ensure patient safety. The choice of solvents used in manufacturing processes is carefully considered to minimize potential risks. Process development aims to reduce or eliminate the use of Class 1 and Class 2 solvents where possible, or to ensure their removal to acceptable levels.