The second revision of the guidance, unveiled Wednesday, is part of the US Food and Drug Administration’s (FDA) attempt to assist abbreviated new drug application (ANDA) sponsors in understanding what deficiencies may cause FDA to refuse to receive (RTR) an ANDA.
The guidance features certain recurrent deficiencies that in FDA’s experience have led to an RTR decision, which FDA says means that an ANDA is “not substantially complete.” The guidance also describes how FDA will assess deficiencies identified during its filing review to determine whether an ANDA should be received.
As outlined in September as part of its Generic Drug User Fee Act (GDUFAII) reauthorization plans, FDA says it provides applicants with the opportunity to correct minor deficiencies or amend an ANDA within seven calendar days. If the requested information is not received within this time, FDA says it will RTR the ANDA.
And if FDA determines that an ANDA contains 10 or more minor deficiencies or one or more major deficiencies, FDA will not consider the ANDA to be substantially complete.
However, the number of ANDA submissions that have received an RTR decision have been minimal over the last several years, especially compared to the 1,725 complete response letters issued for ANDAs in 2016 alone.
Between Fiscal Years 2013 and 2015, FDA refused to receive 379 ANDAs for reasons other than a failure to pay a GDUFA fee. Of all original ANDA submissions, FDA refused to receive: 14% of ANDAs in FY 2013, 10% in FY 2014 and 14% in FY 2015.
As a point of clarification, the agency notes that when a particular deficiency in an ANDA is found, FDA will RTR the ANDA, but the guidance does not establish an obligation for FDA to RTR the ANDA.
“It is important to understand that these statements do not create legal obligations, on applicants or on FDA, but rather are included for purposes of transparency,” the guidance says. “This means that FDA, in the normal course, will RTR an ANDA on the grounds described in this guidance. This guidance does not preclude the possibility that an ANDA applicant may be able to demonstrate, in particular circumstances, that the regulatory requirements for receiving an ANDA have been met even when, as described in this guidance, FDA would in the normal course find the application not sufficiently complete to permit a substantive review and RTR it.”
In August, FDA also finalized guidance regarding serious deficiencies in impurity information that may cause FDA to RTR an ANDA.