FDA’s Office of Generic Drugs Continues to Churn Out New and Revised Policies; Wants to Partner With Industry to Develop Best Practices

August 18, 2014

By Kurt R. Karst –      

The folks in FDA’s Office of Generic Drugs (“OGD”) have been especially busy as of late preparing for the October 1, 2014 implementation of the review and performance metrics agreed to under the Generic Drug User Fee Amendments of 2012 (“GDUFA”).  The Office continues to make personnel changes in preparation for the big event (see here), and has been pumping out policy and guidance documents faster than we can keep up with them.

Earlier this month, OGD issued two important Manual of Policy and Procedures (“MAPPs”) documents for managing the ANDA review queue: (1) MAPP 5200.4, Criteria and Procedures for Managing the Review of Original ANDAs, Amendments and Supplements; and (2) MAPP 5240.3 (Rev. 1), Prioritization of the Review of Original ANDAs, Amendments, and Supplements.  The documents convey OGD’s reworked prioritization schedule for ANDAs in light of GDUFA.  Under the revised policy, ANDAs will be prioritized and considered for expedited review if they meet the specifics of one or more various categories:

  1. Submissions containing patent certifications pursuant to 21 CFR 314.94(a)(12), including the following circumstances in which priority review may be granted:
    • Potential first generic products for which there are no blocking patents or exclusivities on the reference listed drug may receive expedited review; 
    • Submissions that contain a Paragraph IV certification, but become eligible for approval during the review period as a result of no blocking patents or exclusivities (including 180-day exclusivity) and no applicable stays; and 
    • Submissions that contain a Paragraph IV certification, that are submitted on the first day that any valid Paragraph IV application for the drug in question is submitted, and that are received as substantially complete.
  2. Submissions related to drug shortages
  3. Submissions that are subject to special review programs such as the President’s Emergency Plan for AIDS Relief
  4. Submissions related to public health emergencies
  5. Submissions related to certain government purchasing programs
  6. Submissions subject to statutory mandates or other legal requirements
  7. Supplements for which expedited review is requested under 21 CFR 314.70(b)(4)

OGD has also been – and will continue to be – busy issuing new guidance documents explaining current policies and procedures in the post-GDUFA world of ANDA review and approval.  In a notice that will be published in the Federal Register later this week, OGD announced a public hearing on GDUFA implementation that will be held on September 17, 2014, from 9 AM to 5 PM.  In the notice, FDA is soliciting comment on five guidance documents, some of which have yet to see the light of day:

The notice follows a January 2014 notice (see our previous post here) in which FDA announced the establishment of a public docket (Docket No. FDA-2014-N-0032) to receive input and suggestions on ways to improve the quality of ANDAs (original, amendments, and supplements) submitted to OGD and on how to best communicate those suggestions to the generic drug industry.  Thus far, FDA has received only a handful of comments in response to the solicitation.

In addition to canvassing for comments on OGD GDUFA guidances and future policy priorities, the September public hearing will tackle “GDUFA Implementation Related to Generic Drug Exclusivity” and “GDUFA Implementation and Potential First Generics.”  The second topic relates to the two MAPPs discussed above.  According to FDA:

Subsequent to GDUFA’s enactment, FDA has received numerous individual stakeholder comments on what should qualify as a first generic ANDA for the purposes of expedited review.  These comments reflect a range of options, for example, from a broad definition that would prioritize review of all ANDAs for each strength of a Reference Listed Drug submitted for which there is not already an approved ANDA at the time of submission, to a more narrow definition under which only ANDAs that contain a paragraph IV certification and qualify as a “first applicant” under section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act would be designated as a first generic eligible for expedited review.  In addition, several stakeholders have indicated that depending on the criteria FDA applies, first generic status could or should change over time based on other external factors, for example, withdrawal or rescission of approval of another applicant’s ANDA, or shifts in the patent or exclusivity landscape (for example, an unsuccessful patent challenge).

As such, FDA wants to hear from industry as to what specific criteria should FDA apply to identify an ANDA as a first generic eligible for expedited ANDA review, and whether there are there other topics related to first generics eligible for expedited review that require further consideration.

Moving on to “GDUFA Implementation Related to Generic Drug Exclusivity,” FDA is seeking to get a better handle on the topic that generates the most controversy under Hatch-Waxman and in the generic drug industry: 180-day exclusivity.  The current system FDA follows, under which 180-day exclusivity decisions are typically made at the last possible moment (and that sometimes result in a non-decision decision – e.g., 180-day exclusivity “punts” under the failure-to-obtain-timely-tentative-approval forfieture provision), is not optimal.  It is a drain on industry and FDA resources, and can lead to court fire drills.  So, FDA is considering building a better model, and wants to hear industry input on various questions:

  1. Should FDA’s consideration of eligibility for 180-day exclusivity for a specific drug product be a public process, including consideration of whether a first applicant has forfeited its eligibility for exclusivity under section 505(j)(5)(D) of the FD&C Act? If a public process is advisable, would it be so in all instances, or is there a subset of circumstances in which the process should be public?  Also, what administrative mechanisms would best facilitate such a process?
  2. Legal challenges to FDA’s decisions on 180-day exclusivity often must be resolved on an expedited basis which can be inconvenient for the parties and the court. What legal or regulatory mechanisms, if any, are available to better facilitate FDA’s determination of and orderly resolution of sponsors’ challenges to 180-day exclusivity determinations?
  3. Are there other topics related to 180-day exclusivity on which you would like to comment?
  4. Are there topics related to 180-day exclusivity that would benefit from FDA guidance?

Elsewhere, and in the more informal context of FDA’s “From a Clinical Perspective” pubication, the Agency is seeking comment on the five generic drug regulatory science priorities for Fiscal Year  2014: (1) post-market evaluation of generic drugs; (2) equivalence of complex products; (3) equivalence of locally acting products; (4) therapeutic equivalence evaluation and standards; and (5) computational and analytical tools.  Those topics were laid out last year consistent with the GDUFA goals document.