Two GDUFA Guidances Announced in the Federal Register and Published On CDER’s Web Page

The FDA announced the availability of two Guidance documents – on Prior Approval Supplements (here) and the other concerning Easily Correctable Deficiencies (ECDs) (here).  These eagerly anticipated documents have also published on the CDER web page (here) and here.

The FR notice states relative to the Prior Approval Supplements (PAS) Guidance that “this draft guidance is intended to assist applicants preparing to submit to FDA PASs and amendments to PASs for abbreviated new drug applications (ANDAs). It describes FDA’s performance metric goals for PASs and clarifies how FDA will handle a PAS and amendments to a PAS for an ANDA subject to the GDUFA performance metric goals.” 

For the ECD Guidance, FDA notes that “[T]his draft guidance describes how FDA intends to classify major amendments, minor amendments, and easily correctable deficiencies (ECDs). Specifically, the draft guidance defines the types of amendments and describes the GDUFA performance metric goals for the amendment tiers, the process for submitting amendments, and dispute resolution procedures regarding amendment classifications.” 

Due to the complexity of each Guidance document, they will be addressed in separate blog posts.  Please review each Guidance document carefully as applying an inappropriate submission strategy or submitting multiple amendments to submitted supplements could cost you precious time in the review queue in terms of extension of the review clock.

Rather than report what we already know about how the Agency will handle PAS submissions under GDUFA, let’s concentrate on the subtle points made in the document.

For instance, we should all know about the GDFA goals for supplements submitted in FY 2015-2017 and the percent of OGD’s commitment that rises by cohort year from 60% to 75% to 90% in 6 months or 10 months (if an inspection is needed), but did you realize that the Refuse-to-Receive (RTR) provisions apply to all PAS submissions?  If your application is not received, you lose 25% of your user fee and must submit a new fee upon resubmission.  Also, if you submit a supplement as a CBE or CBE-30 and FDA decides it should be a PAS, and then FDA will send you a letter telling you that and will administratively withdraw your CBE-type supplement.  No goal date will be established until the supplement is resubmitted as a PAS with a paid fee and goes through the RTR evaluation.  The submission date will be the date the new PAS supplement hits the electronic gateway (if it is ultimately found acceptable for review).

Also, goal date can change based on amendments submitted to the supplement or the need for inspection.  The Guidance discusses Tier 1 Major and Minor Amendments in response to a Complete Response Letter (with dates of from 6 months for a Tier 1 Minor to 10 months for a Tier 1 Major Amendment), but 5 or more Tier on Minors or Tier 2 or Tier 3 amendments have a much greater impact and could (in certain instances) remove the PAS from a GDUFA goal date.

The Draft Guidance also discussed grouped supplements (multiple supplements for the same CMC or other change) and notes that each is handled as a single supplement as far as user fees go.  So, if you submit a group of 10 such supplements, each will require a fee.  If the fee is only paid for the lead supplement, the other 9 will not be received.  FDA indicates that a comparability protocol may be submitted for one of the group with one fee paid and then, if the Agency approved the protocol, the remainder of the supplements may be submitted based on the reduced filing type agreed to in the comparability protocol, with no fee required for the permitted CBE or CBE-30 supplements under the approved comparability protocol.

FDA also notes that they will apply a risk-based evaluation of the need for inspection based on both previous inspections (finished dosage forms – 2 year window, APIs – 3 year window and testing labs – 4 year window) and, if a PAS is submitted and an initial goal date of 10 months is assigned, because FDA believes an inspection is needed but later decides an inspection is not needed, the goal date will be changed from 10 months to 6 months and the applicant will be so notified.

If any facilities named in the application of affiliated facilities have not paid their fees and appear on the arrears lists or have never paid a fee, the supplement will not be received, so please be sure that any referenced facility or their affiliates are up to date on their required GDUFA fee payments.  Also remember that payment of fees only apply to supplements submitted to ANDAs and not NDAs or BLAs and only apply to supplements originally submitted after October 1, 2012 and goal dates apply only to supplements submitted on or after October 1, 2014.

There are lots of nuances contained in the Guidance document and FDA has a webinar prepared and available for each of the guidance documents it issued today, which can be found here. If you need assistance sorting through the requirements and potential landmines associated with this or other GDUFA guidance documents, please be sure to contact Joan Janulis at j.janulis@lachmanconsultants.com. We look forward to assisting you with any questions you may have or in dealing with the Agency on your behalf, if necessary.