Residual Solvents

Residual solvents in pharmaceutical products are defined as organic volatile compounds that are used or produced in the manufacturing of drug substances or excipients, or in the preparation of drug products, or from packaging and storage. Residual solvents are sometimes crucial in the synthesis of drug substances. Oftentimes, residual solvents are necessary to ameliorate the quality of drug substances or excipients. However, they are pitfalls and have no therapeutic value. Therefore, if the residual solvents are not completely removed by practical manufacturing methodologies, they must be evaluated and justified. Pharmaceutical products should contain low levels of residual solvents as determined by safety data. If the presence of residual solvents in pharmaceutical products exceeds tolerance limits as determined by safety data, they may be harmful to the human health and to the environment. That’s the reason that residual solvents testing becomes one of the important parts of quality control in pharmaceuticals. Contract Pharma Analytical Services providers offer residual solvent analysis programs for drug substances (APIs), drug products and excipients utilizing the U.S. Pharmacopeial Convention guideline (USP 467) for the design of its residual solvent studies. Individual customized programs are available. Residual solvent analysis is a very important QC procedure in the pharma industry. Sampling is typically performed by static headspace and analysis is done by GC/FID (flame ionization detector) using a dedicated column. GC/MS (mass spec) can also be used for residual solvent analysis. There are 3 classes of solvents: Class 1, 2 and 3. Class 3 solvents have a low toxic potential to humans. No long-term toxicity or carcinogenicity data are available for many of these substances. Class 2 solvents are non-genotoxic animal carcinogens. Solvents in this class should be limited in pharmaceutical products because of their inherent toxicity. Class 1 solvents (carcinogens) are strongly suspected of being both harmful to humans and environmental hazards. If possible, they should be avoided or at the least have their levels controlled. Testing of drug substances, excipients, and drug products for residual solvents should be performed when production or purification processes are known to result in the presence of such residual solvents. It is only necessary to test for residual solvents that are used or produced in the manufacture or purification processes.