USFDA has issued a guidance intended to assist applicants preparing to submit FDA abbreviated new drug applications (ANDAs) and prior approval supplements (PASs) to ANDAs for which the applicant is seeking approval of a new strength of the drug product. The guidance highlights deficiencies that may cause FDA to refuse to receive (RTR) an ANDA.
 
An RTR decision indicates that the regulator has determined that an ANDA is not substantially complete. But a substantially complete ANDA is sufficiently complete to permit a substantive review. According to the regulatory authority, the guidance is not meant to be a comprehensive list of the deficiencies that may or will lead to an RTR determination by FDA. Instead, it identifies certain deficiencies and certain recurrent deficiencies that in the regulator’s experience has led it to refuse to return an ANDA.
 
Further, the guidance also describes how FDA will assess deficiencies identified during its filing review to determine whether an ANDA should be received.
 
The regulatory authority indicated that pursuant to the enactment of the Generic Drug User Fee Amendments of 2012 (GDUFA), the Office of Generic Drugs (OGD) is tasked with a number of activities, including the development of enhanced refusal to receive standards for ANDAs and other related submissions by the end of year .
 
Enhanced RTR standards are important because the practice of submitting an ANDA that is not sufficiently complete to permit a substantive review and then ‘repairing’ it in the course of an extended review period that needs several cycles of FDA response and applicant repair is inherently inefficient and wasteful of resources. In addition, ANDAs that are not sufficiently complete to permit a substantive review generate extra reviews and letters.
 
FDA evaluates each submitted ANDA individually to determine whether it can be received. The receipt of an ANDA means that FDA made a threshold determination that it is a substantially complete application.

FDA determines that an ANDA contains ten or more minor deficiencies or one or more major deficiencies. The regulator will not consider the ANDA to be a substantially complete application under 21 CFR 314.101(b)(1).
 
If the applicant decides to submit additional materials to correct the deficiencies, the resulting amended ANDA will be considered a new submission.
 
If an ANDA is not received and the applicant takes no action, the regulator could consider the ANDA withdrawn after 1 year. An ANDA applicant’s failure to take action after a refuse-to-receive decision on an ANDA may be considered a request by the applicant to withdraw it, unless the applicant requests an extension of time in which to resubmit the same.
 
There may be circumstances, however, under which an exception to, or a waiver of, a regulatory requirement may be granted. FDA will consider the merits of such circumstances on a case-by-case basis, stated the guidance.