Lack Of Priority? No ANDAs Approved Using Expedited Pathway In FY 2018
Executive Summary
US FDA also refused to receive many priority generic drug applications, suggesting the expedited pathway may not be working as intended quite yet.
The US FDA did not approve any priority assessment ANDAs in fiscal year 2018, but did push a few applications through another expedited pathway, signaling that industry may not fully understand the new system intended to help speed generic drugs to market.
Priority assessments were introduced in 2017 as part of the FDA Reauthorization Act. Under the pathway, sponsors can receive an eight-month assessment goal, as opposed to a 10-month standard goal.
The new expedited path has yet to see any generic applications approved. Throughout FY 2018, none were reported, although several applications appeared to be pending.
Robert Pollock, senior advisor and outside director to the board of Lachman Consultants, speculated that the lack of priority approvals indicate "either the program is too new to generate any approvals or is not working like [the Office of Generic Drugs] thought."
FDA seemed to agree, indicating there was not much time for many priority applications to travel the pathway. The agency told the Pink Sheet "the earliest eight-month goal date would be in June 2018, only four months prior to FY 2018 closing."
"The only three applications meeting this criteria were reviewed and acted on within the shorter goal date. However, they received a complete response letter," the agency said. "FDA is optimistic that approval numbers, specifically first cycle approval numbers, will increase with time as more high quality applications are submitted."
In late October, FDA posted data indicating one priority application was approved during the July-September quarter. FDA said that was a mistake and corrected it Nov. 1 to indicate there were no priority approvals.
There could be much more priority assessment activity during FY 2019. FDA data indicates there were 29 priority ANDAs awaiting FDA action and three others awaiting sponsor action during the July-September quarter.
Attorney Kurt Karst, director at Hyman, Phelps and McNamara, told the Pink Sheet he expected more priority approvals in the first year, but said it may take the agency and industry more time to understand the pathway.
Industry also may remain shy about using the pathway because of its requirements, namely that facility information must be submitted 60 days before the ANDA for FDA to determine inspection plans.
In FY 2018, the agency received 67 pre-submission facility correspondence, the letter required in advance of the priority ANDA, likely indicating priority applications were a small fraction of the 1,044 ANDAs submitted overall.
The low numbers of priority application may also indicate industry dissatisfaction with the current structure of the pathway. Some sponsors have complained that if facility information was ready 60 days before the planned filing date, they would not wait to submit, essentially rendering the shortened review meaningless. (Also see "New ANDA Review Pathways: Should You Be A Priority Or Expedited?" - Pink Sheet, 13 Nov, 2017.)
Priority Applications A Significant Portion Of Refused Submissions
Some priority applications also seem to be fundamentally flawed upon submission and cannot be reviewed, which may further discourage use of the pathway.
FDA data indicates 44 priority applications submitted since the generic drug user fee program reauthorization were refused to be received. There were 11 more priority application refusals than standard application refusals. (See table.)
The agency told the Pink Sheet that a contributing factor may be that there is a higher volume of priority applications compared to standard applications.
A large portion of ANDAs received qualify for a priority or expedited pathway and the shorter review goal. There also have been questions about whether the priority pathway should be limited to ensure it remains a valuable incentive. (Also see "Will GDUFA III Curtail Priority Assessments?" - Pink Sheet, 14 Sep, 2018.)
|
GDUFA FY 2018 Refuse To Receive Actions |
|
|
Standard-GDUFA II |
33 |
|
Priority-GDUFA II |
44 |
|
GDUFA I |
50 |
|
Total |
127 |
|
Source: FDA generic drug program activity report |
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Two More Competitive Generic Therapies Approved
The competitive generic therapy designation (CGT) was added along with priority review in FDARA, in part to help increase competition and help lower drug prices.
A CGT offers expedited assessment and additional marketing exclusivity for ANDAs approved in areas where there is not more than one approved drug. FDA approved three during the July-September quarter, including methylergonovine maleate tablets 0.2 mg and amphetamine sulfate tablets 5 mg and 10 mg, both from Amneal Pharmaceuticals LLC. They were approved on Sept. 10 and Sept. 26, respectively. Another 45 CGT designated ANDAs were awaiting FDA action and two were awaiting sponsor action during the quarter, according to FDA data.
Apotex Inc.'s potassium chloride oral solution for treatment and prevention of hypokalemia was the first competitive generic therapy approved. (Also see "US FDA’s First Competitive Generic Therapy Approval Comes With A Twist" - Pink Sheet, 9 Aug, 2018.)
First-Cycle Approvals Improved Over GDUFA I
FDA reported 142 full first-cycle approvals during FY 2018, which comprised about 18% of all the full approvals. Another 24 first-cycle tentative approvals were reported, which was about 13% of the FY 2018 total.
The first-cycle full approval figure was an improvement over what was seen during previous years: 11.5% in FY 2015, 14.7% in FY 2016 and about 10% in FY 2017 as of May 1.
FDA said it was pleased with the results and attributed its success to increased communications with sponsors during the initial review cycle through discipline review letters and information requests.
The trend line throughout the fiscal year started high and ended lower, however. In October 2017, the agency reported 26 first-cycle full approvals out of 87 total for the month, a nearly 30% rate. However, the figure never approached that mark again, reaching as high as 20 in December 2017 and 16 in July. The lowest first-cycle full approval monthly total, five, was reported in September. (Also see "GDUFA II Reviews Start Strong With High First-Cycle Approval Rate" - Pink Sheet, 4 Dec, 2017.)
The first-cycle tentative approval trend remained steady throughout the year, ranging in the low single digits each month. FDA reported no first-cycle tentative approvals in September. (See chart below.)
The agency likely will be expected to increase the numbers in FY 2019 and beyond, especially now that the generics program is considered at steady state. Outgoing Office of Generic Drugs Director Kathleen Uhl said in September that submissions are balanced by approval and other actions. (Also see "US FDA's Generics Program Reaches 'Steady State' Milestone" - Pink Sheet, 7 Sep, 2018.)
OGD also set a record for overall full approvals in FY 2018. (Also see "US FDA Sets Generic Approval Record, But Generic Sponsors Aren't Celebrating" - Pink Sheet, 12 Oct, 2018.)