FDA revises guidance on responding to ANDA complete response letters

The US Food and Drug Administration (FDA) has revised its guidance on timeframes for responding to complete response letters (CRL) to abbreviated new drug applications (ANDA) based on commitments in the latest generic drug user fee program. Under the latest deal, minor amendments that have not been addressed within a year of the CRL will be reclassified as major amendments.
 
The agency published the revised guidance on 14 December, only 5 months after first issuing the ANDA CRL guidance. The revision is meant to reflect new commitments agreed upon between the generic drug industry and FDA under the third iteration of the Generic Drug User Fee Amendments (GDUFA III). (RELATED: FDA finalizes ANDA CRL, Orange Book Q&A guidances, Regulatory Focus 27 July 2022)
 
“As described in the GDUFA III commitment letter applicable to this latest reauthorization, FDA has agreed to performance goals and program enhancements regarding aspects of the generic drug assessment program that build on previous authorizations of GDUFA,” the agency said. “New enhancements to the program are designed to maximize the efficiency and utility of each assessment cycle, with the intent of reducing the number of assessment cycles for ANDAs and facilitating timely access to generic medicines for American patients.”
 
Echoing what it said in the previous version of the guidance, FDA notes that it can’t hold incomplete ANDA applications open indefinitely, as the data provided in the application may become outdated and the science the drug is based on may evolve.
 
Typically, the agency gives sponsors a year to respond to a CRL with additional information to support approving the ANDA. If sponsors are unable to meet their obligations within that timeframe, reviewers say they will close the application which means drug developers have to start from scratch unless they can give FDA a good reason for the delay.
 
“If an applicant wishes to continue to seek approval in this manner and determines it will be unable to address the deficiencies within 1 year of issuance of the CRL, the applicant should submit an amendment to its ANDA requesting an extension of time to address those deficiencies,” said FDA. “The applicant should submit its request for an extension on or before the date the response to the CRL is due.”
 
FDA says there are a number of factors it will take into consideration when deciding whether to grant an extension that includes the number of times the company has asked for an extension and their reasoning, extenuating factors outside the sponsor’s control, and whether past extensions were classified as minor or major deficiencies in the CRL.
 
“As described in the GDUFA III commitment letter, FDA will reclassify a minor amendment as a major amendment if the amendment is submitted more than 1 year after the date FDA issued the CRL, unless the ANDA is for a product on the drug shortage list … or is the subject of a response to a Public Health Emergency … or is anticipated to be subject to the same criteria as apply to such a declaration, at the time of submission,” the agency noted.
 
In the appendix of the guidance, FDA lists other key factors it will take into consideration when deciding to extend an ANDA application response to a CRL, including ongoing studies the sponsor is conducting to meet the agency’s requirements, whether the drug application was delayed due to a global health emergency and whether the sponsor is having trouble procuring the active pharmaceutical ingredient from the manufacturer.
 
Guidance