FDA’s recent speed boost in approving generic drug applications is laudable but still way short of the rate industry says is necessary for all pending ANDAs to be made available for marketing.

ANDA reviewers would have to approve nearly four times as many applications per month as they are currently to reach the required volume before the generic drug user fee program expires at the end of September 2017.

The Generic Pharmaceutical Association estimates that the Office of Generic Drugs has to approve 150 ANDAs a month going forward to eliminate its pre-GDUFA backlog. That would result in a likely unrealistic 3,600 approvals over the next two years.

Marcie McClintic-Coates, Mylan NV VP and head of regulatory affairs, said GPhA knows that the figure is a lot, but the group also reminded FDA that it should not forget GDUFA I goals before determining a new set of commitments for GDUFA II.

“Before we’re jumping into what’s going on next, we’ve got to focus on what’s going on now and how do we get our proper baseline,” said McClintic-Coates, who provided GPhA’s position Sept. 29 during the Parenteral Drug Association-FDA Joint Regulatory Conference.

“There’s a lot of money that went into the program, a lot of critical aims. We’ve got to make sure they’re realized before we’re advancing.”

“Our success in this program is going to come down to a simple metric … are we getting generic drug applications approved and generics in the hands of patients faster?" – Mylan's Marcie McClintic-Coates

GDUFA reauthorization talks began Oct. 7, and the ongoing exchange of unpleasantries suggests the discussions between FDA and sponsors could be tense at times ([A#14150813004]).

FDA is negotiating with four industry groups to renew the program Also see "GDUFA II Negotiations: Contract Manufacturers Gain Seat At Table" - Pink Sheet, 6 July, 2015..

FDA said in an Oct. 9 statement to “The Pink Sheet” that it is ahead of schedule in dealing with the pre-GDUFA backlog. It has acted on 80% of the 2,866 applications in the backlog and is near its goal to act on 90% of them by the end of fiscal year 2017.

Of course, that doesn’t mean they'll all be approved. An action is an approval, tentative approval, “complete response” letter or refusal-to-receive.

The agency said it “would welcome finding 150 ANDAs ready for approval per month.”

“But an approval action requires our full confidence in the quality and substitutability of the product,” the agency said. “In some applications in the backlog, multiple cycles of review are required to assure that confidence.”

McClintic-Coates said after the PDA-FDA conference presentation that more of the GDUFA system needs to be implemented before the number of review cycles will begin to decrease.

FDA has found that most ANDAs needed two to five cycles before they were approved ([A#14141205003]).

The agency would like to cut the number of cycles generic applications need to two in the near-term ([A#00150727013]).

Approvals Continue Increasing

In recent months the agency has increased its approval output.

The agency approved 58 ANDAs in August. That's a new record for a monthly total since GDUFA launched, the second set in three months (see chart).

ANDA Approvals By Fiscal Year

Even though FDA has increased its generic drug approvals in FY 2015, it is far from the rate GPhA says is required to clear its backlog of pre-GDUFA applications.

Source: FDA data and public statements

The total number of approvals for the fiscal year through August was 431, with another month remaining. That already is more than the total for FY 2014 and nine less than the total for FY 2013.

The most recent data place OGD’s monthly average for approvals at more than 39 – still a far cry from the 150 a month that GPhA wants. However, if FDA maintains its rate through the end of FY 2017, it would lead to another 940 approvals, or about 470 per year.

Despite the lofty industry expectations, Ted Sherwood, acting director of the OGD Office of Regulatory Operations, was pleased with the pace of improvements. He said during the conference that the agency was slow initially, but investments OGD made in additional personnel and equipment now are beginning to pay off.

OGD reported more approvals between April and July this year than the previous six months combined. The productivity increase appears to be more evidence that the review system is now running at full speed ([A#14150915002]).

Median ANDA Approval Time Dropping

Industry also is encouraged by OGD’s recent progress.

Median review times are set to decrease for the first time since GDUFA launched, although they still are higher than pre-GDUFA levels.

McClintic-Coates said the median ANDA approval time in 2015 is estimated to be dropping to 42 months, which is a major improvement over the 48 months that initially was projected. It also would be a decrease from the 2014 median of 43 months.

ANDA Median Approval Times

Pre-GDUFA: 31 months
2013: 36 months
2014: 43 months
2015: 42 months (projected)

FDA intends to recalculate the median approval times for applications with review goals and without goals, which may show more improvement.

Industry is happy that the figure is improving, but McClintic-Coates said whether it will be an indicator of GDUFA I success remains to be seen.

“Our success in this program is going to come down to a simple metric … are we getting generic drug applications approved and generics in the hands of patients faster under this program or aren’t we?” she said. “We’re still working on it. That’s the answer.”

FDA estimated in FY 2016 budget documents that the median approval time would remain at 42 months through FY 2015 and FY 2016, although it said that projection was conservative ([A#14150210002]).

Median Approval A Difficult Number

Sherwood said once the backlog and non-review goal applications are under control, approval times will be more reasonable.

“Time to approval is going to be slow for a while on the pre-year three because we’re digging deeper and deeper into the backlog,” he said. “As we progress further into year three, four and five, and we start to look at the metrics by the year they’re submitted, that’s when we’re going to start to see this really sort of different system come into play and you’ll see the value of the user fees.”

ANDAs submitted before Oct. 1, 2014, the third year of GDUFA, do not have a formal review goal. A percentage of those arriving after that date must receive an action within 15 months and then ultimately 10 months ([A#00111212020]).

The agency in August approved its first ANDA with a review clock several months before the goal date ([A#14150819008]).

FDA has made a number of changes to its review system and communications policies to help applications move through its system faster.

OGD review staff can notify a sponsor if a major deficiency is found as well as when an approval is near ([A#14141218005]).

The agency also is working on a policy to allow more communication between the sponsor and OGD to avoid refuse-to-receive actions ([A#14151006001]).

ANDA Approval Improvements Reveal Just How Big The Backlog Is

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