FDA Publishes Additional Guidance on Refuse-to-Receive Standards

FDA has released two guidance documents—one final and one draft—relating to the submission of abbreviated new drug applications (ANDAs). In the guidance documents, FDA addresses deficiencies in the ANDA application and new strength prior approval supplements (PASs) that may cause FDA to refuse to receive the submission.

The final guidance, ANDA Submissions—Refuse-to-Receive Standards Guidance for Industry, identifies recurrent deficiencies that have resulted in application refusals. The goal of the guidance is to improve the quality of original ANDA submissions and provide standards for ANDA submittal that would allow the agency to complete a “substantive review” of an application.  Clarification of this kind, according to FDA, would reduce the number of inefficient communications between the agency and applicants, such as extra cycles of reviews and letters. Although most refusals were related to product quality standards and bioequivalence issues, FDA believes the new guidelines will help applicants successfully avoid major application deficiencies and extended review periods.

The draft guidance, ANDA Submissions—Refuse to Receive for Lack of Proper Justification of Impurity Limits, specifically highlights deficiencies as they relate to impurities and impurity limits that may lead to a refuse-to-receive determination from FDA. The guidance describes the typical deficiencies that lead to a refuse-to-receive decision, including failing to provide adequate justification for proposed limits for specified identified impurities that are above qualification thresholds, proposed limits for specified unidentified impurities that are above identification thresholds, and proposed limits for unspecified impurities.