FDA Guidance for Industry: ANDA Submissions

July 25, 2018 Suzanne Konigsberg

By: Juliane Foley, Senior Consultant

FDA Guidance for Industry: ANDA Submissions – Amendments to Abbreviated New Drug Applications under GDUFA is now finalized.  The majority of the content is identical to the October 2017 Draft Guidance, so those of you who have committed that content to memory, your learning is nearly done.  Below are the handful of the noteworthy differences between the October 2017 draft and the July 2018 final guidance:

  1. For unsolicited amendments clarification was provided that FDA will classify these as major and minor based on the content of the amendment.
  2. For Requests for Final Approval, FDA urges Industry to consider changes needed like RLD labeling changes or updates to the USP, and to consider the associated review goals that will be assigned.  Take home message -- be sure you file the request early enough to avoid delay in ANDA final approval as goal dates will be assigned based on the content of the request. 
  3. Reference to “FDA review” was updated to “FDA assessment” in a few places in alignment with earlier communicated changes made to enhance operational efficiencies.
  4. “Failure to provide analytical methods or method validation” was removed from the list of major deficiencies, likely because this would be an ANDA filing deficiency rather than a major amendment deficiency.
  5. The example of a major deficiency related to extractables and leachables was moved from the microbiology section and relocated to the process section.
  6. A new example of a major deficiency was listed for microbiology regarding reference to an inadequate DMF.
  7. For major deficiencies related to facilities clarification was added that it will be a major deficiency if one or more facilities were found inadequate at the time of action and also if the submission fails to identify a facility that is required to be listed.
  8. Lastly, only Section B “When is an amendment classified as major?” of the now superseded Major, Minor, and Telephone Amendments to Abbreviated New Drug Applications, December 2001 Guidance is included in Appendix B instead of the entire guidance. 

For those who have yet to commit the October 2017 Draft Guidance to memory, below are some useful tips:

  1. Complex GDUFA I tier system is out, standard vs priority reviews are in.
  2. Any submission after an ANDA is received for filing is an amendment.
  3. Information Requests (IR) and Discipline Review Letters (DRL) do not stop the clock so there is no associated goal date.
  4. If a response to an IR or DRL includes information not requested, or more information than anticipated, FDA will classify the response as major or minor and assign a review goal date.
  5. Even a minor GMP issue with a facility is now considered a major deficiency.
  6. Unsolicited amendments will be classified as major or minor based on this guidance.  When an unsolicited amendment is filed, FDA will assign the later of the amendment goal date or the ANDA goal date.  Take home here is that minor and early unsolicited amendments may be more palatable to a sponsor than later and/or major unsolicited amendments, in terms of avoiding an extension of ANDA time to approval..  Also note that FDA may defer the review of an unsolicited amendment if their reviews are near completion, meaning that FDA could choose to review the information in the amendment when you respond to a CRL.
  7. Table 1 pasted below is useful as it clearly outlines the goals for major and minor amendments.  And don’t forget that to meet the goal, FDA needs to “act” which means a refuse to receive, an approval, a tentative approval, or a complete response letter.

  1. Table 2 pasted below clearly outlines the goals for major and minor amendments to Prior Approval Supplements (PASs).  

  1. Appendix A is also extremely useful as it lists example major deficiencies.  For those that might want to go after that first cycle ANDA or PAS review, be sure none of these exist before you submit!


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