If you think the just-issued prior approval supplement (PAS) Draft Guidance was complex, wait until you read this one! Entitled “ANDA Submissions – Amendments and Easily Correctable Deficiencies under GDUFA”, the document:
- Describes the Tier system for the different types of amendments
- Explains how different types of amendments may affect the application’s original review dates
- Explains FDA’s performance metric goals based on the different amendment Tiers
- Explains the process for submitting amendments
- Describes the request for reconsideration process for FDA classification decisions
Quite interestingly, the Draft Guidance notes that “[I]n accordance with a Commitment Letter that accompanied the legislation, FDA agreed to certain performance goals and procedures for the review of amendments submitted electronically to original ANDAs and PASs filed on or after October 1, 2014. The performance goals do not apply to amendments submitted on or after October 1, 2014, if they amend original ANDAs or PASs submitted before October 1, 2014.” That is not consistent with what we thought relative to amendments submitted prior to those dates, and that may be further bad news for cohort year one and two GDUFA amendment submissions.
GDUFA goal dates for amendments are classed into three tiers, 1, 2 or 3 with goal dates ranging from 3 months to no goal date, depending on the classification of the tier of the amendment and whether they are solicited or unsolicited, major or minor or administrative. The Guidance document has a nice table reproduced below that outlines the Goal dates for the various tiers and types of amendments.
The document also defines a solicited and unsolicited amendment (which are responses to Complete Response Letters [CRL] or information submitted not in response to a CRL) , a major and minor amendment, easily correctible deficiencies, delaying amendments (caused by a third party, e.g., label update by NDA holder, update to USP monograph), non-delaying amendments (not requested by FDA or the result of the action of a third party), and administrative amendments (e.g., patent amendments, requests for final approval after a tentative approval letter with no additional scientific review required).
The document also provides a rather elaborate discussion of the goal dates for the first through thirdTier 1 amendments and those for the 4-5th Tier 1 amendment and also describes how amendments submitted during the review clock of an application will extend the goal date original assigned to the ANDA. Please review the Guidance document for the goal dates based on the appropriate fiscal year. The Tier two amendments have goal dates of 12 months with varying percentages by FY, and Tier 3 amendments have no goal dates. The cohort year of the ANDA (not the amendment submission date) dictates what (if any) GDUFA goal date will apply. Also, please remember that only electronic submissions are subject to GDUFA goal dates, so if you are submitting in paper, plan for a long wait for any FDA action.
Tier two amendments submitted after a CRL but before the applicant makes its complete response will be deferred until the complete response to the CRL is received by OGD.
Please be careful when submitting a request for final approval after a Tentative Approval (TA) letter because, as FDA explains, usually a response to request for final approval will be handled in 3 months if no changes are made to the ANDA since the TA issued, but, if additional data or changes are submitted when requesting final review, a goal date of 12 months may be assigned. This could be fatal to a company’s launch plans, so please be certain how you approach any CMC changes at this time in the process. Perhaps think about submitting changes as a supplement after approval and limp along with the approval requirements as established in the submission at the time of the TA.
Another piece of advice: if FDA issues an ECD letter, be certain to respond within the 10 day time period and do not submit additional information in the amendment; otherwise, the FDA may reclassify the amendment and place a longer goal date on it depending on how it reclassifies the response. FDA will notify the applicant of any change and there is an appeal process of such decisions to reclassify an amendment type and subsequent goal date change described in the draft document. FDA also described how it may treat amendments and submissions of poor quality and also notes that, at its discretion, it may not reclassify an amendment type if it may result in the application losing its goal date; so, to avoid any unpleasant surprise,s assure your submissions are of high quality.
The FDA is placing another relevant burden on applicants to assure proper coding in FDA management occurs and is requiring firms to properly identify they type of submission clearly on the cover letter (see section V of the document for details). Failure to follow the FDA recommendations in this section could further delay your submission’s review.
Appendix A of the document provides examples of Major Amendments for the various types of submissions (e.g, DMFs, CMC, bioequivalence, microbiology etc.) and Appendix B provides examples of Minor Amendments for the various disciplines. Appendix C provides examples of easily correctible deficiencies. Appendix D provides a handy amendments flow chart. As noted above, this guidance document is quite complex and must be read in the context of each submission you make. Please contact Joan Janulis at firstname.lastname@example.org if you need help in navigating any of the issues described in this document.