ANDA Stress Test: End-Of-Year Submission Bolus Pressures US FDA Review System
Executive Summary
As more generic applications arrive, Office of Generic Drugs staff may have a tougher time reaching review goals.
FDA 's generic drug workload increased substantially in December and may provide a stress test of sorts for its enhanced review system and approval pace.
Sponsors submitted 235 abbreviated new drug applications in December, the most received in a single month since the famous June 2014 avalanche when 635 ANDAs arrived. While sponsors tend to push more applications in December than normal to close out their calendar years, the 2016 number is unusually high. In December 2013, there were 225 ANDAs submitted, but throughout the generic drug user fee program era, no other December rush has approached the 2016 total (see box).
December Monthly ANDA Submission Totals
- 2012: 163
- 2013: 225
- 2014: 43
- 2015: 180
- 2016: 235
Industry now has submitted 424 ANDAs through the first quarter of fiscal year 2017 and is on pace to send nearly 1,700 ANDAs for the entire fiscal year. That total would break the GDUFA record for annual submissions set in FY 2014 (the year of the avalanche) when FDA received 1,473 submissions (see charts below).
The growing total likely will increase the pressure on FDA's ANDA review staff to meet its GDUFA goals, in addition to gain better control of its workload. Under the generic user fee program, nearly all of these new submissions, 90%, are scheduled to receive a first action (which can be an approval, tentative approval, refuse-to-receive, or complete response) within 10 months. (Also see "GDUFA Performance Goals For Fiscal Years 2013-2017" - Pink Sheet, 12 Dec, 2011.)
Source: FDA Generic Drug Program activity report data
The 10-month clock is the most aggressive review goal of GDUFA so far. As more sponsors look to take advantage, the agency may have a tougher time moving the applications through its systems within the required time. The Office of Generic Drugs wants to maintain its workload at a steady state, but it does not appear it has reached it yet. (Also see "Dark, Then Dawn: ANDA Workload Approaching Steady State After 2014 Eruption" - Pink Sheet, 28 Mar, 2016.)
OGD also does not want the applications under review confused with the official GDUFA backlog, however. Agency officials have argued that a number of applications remain pending because industry has yet to respond to FDA questions or requests. (Also see "FDA Aims To 'Pierce The Rhetoric' On Generic Application Backlog" - Pink Sheet, 31 Oct, 2016.)
This latest bolus also may spark concerns that FDA once again will be sending more refuse-to-receive or complete response actions in the coming months because a number of applications are incomplete or otherwise not approvable. After a bolus in December 2015, the agency refused a substantial proportion of the applications. (Also see "Generic Reviews Steaming Ahead, But Are Storm Clouds On The Horizon?" - Pink Sheet, 24 Feb, 2016.)
However, there seem to be some signs that application quality may be improving. The agency has seen its refuse-to-receive actions decrease significantly in FY 2017, suggesting that more ANDAs may include all the necessary information. (Also see "Generic Application Quality Showing Signs Of Improvement" - Pink Sheet, 4 Jan, 2017.)
Why All The ANDAs Now?
Ultimately, it may be hard to define a specific cause of this ANDA rush. The FY 2014 avalanche was triggered in part by sponsors’ efforts to avoid enhanced stability requirements that were set to go into effect. (Also see "ANDA Avalanche: How Will FDA Deal With The 600 Received This Month?" - Pink Sheet, 30 Jun, 2014.)
When the FY 2017 submission wave began, it was suspected that sponsors were most interested in the 10-month review clock, which was five months faster than the 15-month clock promised the previous fiscal year. (Also see "ANDA Submission Wave Continues; Is A Crest Near?" - Pink Sheet, 12 Dec, 2016.)
FDA told the Pink Sheet that it is committed to meeting its obligations under GDUFA, "but we cannot speculate about apparent short-term submission trends and what effect those may have on the review process."
Brian Malkin, senior counsel at McGuireWoods, said a reason for the rush is difficult to determine because there are a lot of unknowns about what changes will be made by President-elect Trump and the renewed generic drug user fee program.
Trump has promised to shake up the federal bureaucracy, including FDA. A few names have been floated for FDA commissioner, who may have different views than Robert Califf, who is expected to depart in the coming days. (Also see "US FDA Might Be Temporarily Headed By Ostroff As Califf Sets His Departure" - Pink Sheet, 5 Jan, 2017.)
Further on in 2017, FDA might see another end of fiscal year slowdown and then surge in October, since GDUFA II is slated to make several changes, including creating a priority review pathway (Also see "ANDAs Can Get Priority, Eight-Month Reviews Under User Fee Deal" - Pink Sheet, 24 Sep, 2016.) and allowing pre-submission meetings for complex product sponsors. (Also see "Complex ANDAs To Be Allowed Pre-Submission Product Meetings" - Pink Sheet, 24 Oct, 2016.)
Approval Pace Remains Robust
Despite the submission bolus, the agency continued its elevated approval pace.
FDA posted 56 full approvals in December, which is in line with the average for the first two months of the fiscal year. The agency now has cleared 169 ANDAs through three months and is on pace to notch 676 for the full fiscal year.
It would surpass the record total of 651 set in FY 2016. (Also see "ANDA Approvals, Complete Responses Hit Record In FY 2016" - Pink Sheet, 12 Oct, 2016.)
The agency also has issued 47 tentative approvals through the first quarter of FY 2017, or 15.7 per month, which is slightly ahead of its FY 2016 pace of 15.3 per month.
Elevated approval levels could generate some attention going forward as the drug pricing debate continues. Congress and other stakeholders have been pushing FDA to approve generics faster to add pricing pressure. (Also see "Could Drug Price Spikes Spur ANDA Priority Reviews?" - Pink Sheet, 28 Jan, 2016.)