Posted: 25 Feb 2016 09:32 AM PST
By Kurt R. Karst –
Earlier this week at the Generic Pharmaceutical Association’s (“GPhA”) annual meeting in Orlando, Florida, Dr. Kathleen (“Cook”) Uhl, Director of the Office of Generic Drugs (“OGD”), gave the keynote address, providing the generic drug industry with a much-anticipated lowdown on FDA’s progress in implementing the Generic Drug User Fee Amendments of 2012 (“GDUFA”). According to Dr. Uhl’s facts and figures (there’s no fiction in them, she noted to the packed audience), OGD has made significant headway on improving communication and increasing productivity. (According to Dr. Uhl, this is due primarily to OGD’s improved IT system for the generic drug program that was put in place in October 2014.)
Dr. Uhl’s presentation covered five topics: (1) GDUFA Update; (2) Output & Productivity; (3) Quality of ANDA Submissions; (4) Update on Pre-Year 3 Cohort; and (5) Opportunities for Improvement & Challenges. We’ll focus on topics (2)-(4) as they tend to be of the greatest interest to ANDA applicants. For a point of reference, and as background, we refer folks to the GDUFA I Program Performance Goals and Procedures. (GDUFA II is currently being negotiated. FDA has already held several negotiation sessions andstakeholder meetings.)
Output & Productivity
Output is really where the rubber meets the road under GDUFA. After all, that’s what the generic drug industry is paying user fees for in the first place: to increase generic drug availability with a greater number of ANDA approvals must faster than in the pre-GDUFA era. Of course, high output depends on high quality input (we’ll get to that topic a little later). By the end of GDUFA Year 5 (Fiscal Year 2017), when OGD is expected to review and act on 90% of original ANDAs within 10 months from the date of submission, OGD anticipates that a typical 10-month review cycle will follow the timeline below.
But we’re not quite at this timeline yet! So where are we?
After an initial two years of high volume submission numbers (GDUFA Years 1 and 2; FYs 2013 and 2014), ANDA submissions tapered off in FY 2015, as shown in the tables below. (Although the second table below reflects submissions through September 2015, there was an increase in submissions in the first quarter of FY 2016 (GDUFA Year 3), with 180 ANDA submissions in December 2015 alone.)
FDA’s various actions on ANDAs – final approvals, tentative approvals, and complete responses – have been pretty consistent over the first three FYs of GDUFA, though the number of Complete Response Letters has increased dramatically compared to FY 2012. The increase is due to a large number of Complete Response Letters for pre-GDUFA backlog ANDAs, as shown in the second table below. As shown in the third table below, FY 2016 has gotten off to a tremendous start, with 99 final and tentative approval actions in December 2015. That’s the highest number of final and tentative approvals ever issued in a single month.
In other good news, Dr. Uhl reported that OGD has eliminated the Office’s backlog of ANDAs requiring a filing decision, which stood at two ANDAs in December 2015. Today, ANDA filing (receipt) decisions are being made in about 31 days.
Quality of ANDA Submissions
Dr. Uhl laid out various metrics for ANDA quality, including the first peek at GDUFA Year 3 (FY 2015) ANDA actions. ANDA Refuse-to-Receive (“RTR”) continue to be a problem, with hundreds of ANDAs being issued RTR letters each fiscal year, as shown in the table below. In fact, of the 180 ANDA submissions made in December 2015, approximately 30% of them were issued RTR letters, primarily for insufficient stability information and/or insufficient dissolution information). Although the RTR numbers provided by Dr. Uhl are generally in line with the Refuse-to-File numbers for applications submitted to FDA during the first few years of PDUFA implementation, the ANDA RTR numbers should be lower. Many of the RTR letters could have been avoided with closer scrutiny of the submission.
In addition, the number of ANDA review cycles – and, in particular, CMC review cycles – remains high. Very few applications are approved after the initial review cycle.
Moving on to the first numbers provided by FDA for ANDAs submitted in FY 2014 (GDUFA Year 3), only 12% of the 51 ANDAs with a 15-month action date that fell in January 2016 received a first cycle approval (or tentative approval). Most of the submissions were the subject of a Complete Response Letter. Of course, that’s only 1 month of data, so folks should not be overly concerned . . . . yet. By way of comparison, 36% of applications were approved under the first cycle in the first year of PDUFA (FY 1993).
Update on Pre-Year 3 Cohort
With respect to pre-year 3 GDUFA ANDAs, the details are a little sketchy. Although we know generally where things stand with pre-Year 3 applications, thanks in large part to FDA’s recent launch of the Generic Drug Review Dashboard, we don’t have much insight into FDA’s ability to meet internal goals set for those applications. Those internal (and aspirational) goals, known as Target Action Dates (“TADs”), were created by FDA to give industry comfort that review of their applications would not suffer as a result of OGD’s need to meet goals for applications submitted post-year 2. TADs also serve as a sort of dry run for OGD to meet the true goals under GDUFA. The TADs established by FDA are shown in the slide below. Although knowing the various TADs OGD has established are nice, it would be helpful to know OGD’s success rate.
Reminder: Register now for the May 3, 2016 Virginia Tech and HP&M Conference on Effective Documentation. Information on the conference is available here.
Earlier this week at the Generic Pharmaceutical Association’s (“GPhA”) annual meeting in Orlando, Florida, Dr. Kathleen (“Cook”) Uhl, Director of the Office of Generic Drugs (“OGD”), gave the keynote address, providing the generic drug industry with a much-anticipated lowdown on FDA’s progress in implementing the Generic Drug User Fee Amendments of 2012 (“GDUFA”). According to Dr. Uhl’s facts and figures (there’s no fiction in them, she noted to the packed audience), OGD has made significant headway on improving communication and increasing productivity. (According to Dr. Uhl, this is due primarily to OGD’s improved IT system for the generic drug program that was put in place in October 2014.)
Dr. Uhl’s presentation covered five topics: (1) GDUFA Update; (2) Output & Productivity; (3) Quality of ANDA Submissions; (4) Update on Pre-Year 3 Cohort; and (5) Opportunities for Improvement & Challenges. We’ll focus on topics (2)-(4) as they tend to be of the greatest interest to ANDA applicants. For a point of reference, and as background, we refer folks to the GDUFA I Program Performance Goals and Procedures. (GDUFA II is currently being negotiated. FDA has already held several negotiation sessions andstakeholder meetings.)
Output & Productivity
Output is really where the rubber meets the road under GDUFA. After all, that’s what the generic drug industry is paying user fees for in the first place: to increase generic drug availability with a greater number of ANDA approvals must faster than in the pre-GDUFA era. Of course, high output depends on high quality input (we’ll get to that topic a little later). By the end of GDUFA Year 5 (Fiscal Year 2017), when OGD is expected to review and act on 90% of original ANDAs within 10 months from the date of submission, OGD anticipates that a typical 10-month review cycle will follow the timeline below.
But we’re not quite at this timeline yet! So where are we?After an initial two years of high volume submission numbers (GDUFA Years 1 and 2; FYs 2013 and 2014), ANDA submissions tapered off in FY 2015, as shown in the tables below. (Although the second table below reflects submissions through September 2015, there was an increase in submissions in the first quarter of FY 2016 (GDUFA Year 3), with 180 ANDA submissions in December 2015 alone.)
FDA’s various actions on ANDAs – final approvals, tentative approvals, and complete responses – have been pretty consistent over the first three FYs of GDUFA, though the number of Complete Response Letters has increased dramatically compared to FY 2012. The increase is due to a large number of Complete Response Letters for pre-GDUFA backlog ANDAs, as shown in the second table below. As shown in the third table below, FY 2016 has gotten off to a tremendous start, with 99 final and tentative approval actions in December 2015. That’s the highest number of final and tentative approvals ever issued in a single month.
In other good news, Dr. Uhl reported that OGD has eliminated the Office’s backlog of ANDAs requiring a filing decision, which stood at two ANDAs in December 2015. Today, ANDA filing (receipt) decisions are being made in about 31 days.
Quality of ANDA SubmissionsDr. Uhl laid out various metrics for ANDA quality, including the first peek at GDUFA Year 3 (FY 2015) ANDA actions. ANDA Refuse-to-Receive (“RTR”) continue to be a problem, with hundreds of ANDAs being issued RTR letters each fiscal year, as shown in the table below. In fact, of the 180 ANDA submissions made in December 2015, approximately 30% of them were issued RTR letters, primarily for insufficient stability information and/or insufficient dissolution information). Although the RTR numbers provided by Dr. Uhl are generally in line with the Refuse-to-File numbers for applications submitted to FDA during the first few years of PDUFA implementation, the ANDA RTR numbers should be lower. Many of the RTR letters could have been avoided with closer scrutiny of the submission.
In addition, the number of ANDA review cycles – and, in particular, CMC review cycles – remains high. Very few applications are approved after the initial review cycle.
Moving on to the first numbers provided by FDA for ANDAs submitted in FY 2014 (GDUFA Year 3), only 12% of the 51 ANDAs with a 15-month action date that fell in January 2016 received a first cycle approval (or tentative approval). Most of the submissions were the subject of a Complete Response Letter. Of course, that’s only 1 month of data, so folks should not be overly concerned . . . . yet. By way of comparison, 36% of applications were approved under the first cycle in the first year of PDUFA (FY 1993).
Update on Pre-Year 3 Cohort
With respect to pre-year 3 GDUFA ANDAs, the details are a little sketchy. Although we know generally where things stand with pre-Year 3 applications, thanks in large part to FDA’s recent launch of the Generic Drug Review Dashboard, we don’t have much insight into FDA’s ability to meet internal goals set for those applications. Those internal (and aspirational) goals, known as Target Action Dates (“TADs”), were created by FDA to give industry comfort that review of their applications would not suffer as a result of OGD’s need to meet goals for applications submitted post-year 2. TADs also serve as a sort of dry run for OGD to meet the true goals under GDUFA. The TADs established by FDA are shown in the slide below. Although knowing the various TADs OGD has established are nice, it would be helpful to know OGD’s success rate.
Reminder: Register now for the May 3, 2016 Virginia Tech and HP&M Conference on Effective Documentation. Information on the conference is available here.
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