Executive Summary

FDA's Office of Generic Drugs noted in late May that starting July 1, manufacturers must demonstrate in their abbreviated new drug applications that their drugs comply with the residual solvent limits specified under USP Chapter <467>. While the announcement was made by OGD, the new standards will apply to new drug applications as well. The standard covers all compendial drug substances and excipients, or products that have a USP monograph. However, it is expected that FDA reviewers will apply the standard to other NDAs and ANDAs that do not have a USP monograph. The chapter is modeled on the ICH Q3C quality guidance on residual solvents. The OGD announcement notes that after July 1, "any new ANDA must provide information and data as necessary to demonstrate control of residual solvents prior to approval (or tentative approval). ANDAs currently under review, but are not yet approved by July 1, 2008, must also contain this information and data as necessary. Residual solvent information and data as necessary for approved products should be submitted in the next annual report for the ANDA." The standard and the ICH Q3C classify residual solvents into three classes according to their toxicity level. In addition, the standard specifies that sponsors should include a commitment to reassess their compliance with USP <467> if they change ingredient suppliers in the post-approval period, including implementing revised controls. The standard was supposed to go into effect on July 1, 2007, but USP granted a one year-extension to give manufacturers additional time to conform to the new standards