Drug impurities: problems and regulations

The matter of impurities is a frequently debated issue, mainly focused on the validation of the analytical methods and on the toxicology of potential impurities. In the first part of the review, the classification, the source and the chemical aspects of impurities are briefly considered according to the current international regulations. A special attention is given to the analytical control, in both qualitative and quantitative terms, of unexpected impurities arising from changes in the manufacturing process or by degradation. The thresholds for identification and qualification of impurities in new drug substances and in new drug products are examined together with the safety studies, when required. Finally, the acceptance limits for four classes of residual solvents are also reported.