There is no doubt that the Office of Generic Drugs (OGD) is receiving more work than it anticipated under the negotiated GDUFA I program. Dr. Kathleen (Cook) Uhl, Director OGD, noted that OGD received over 5 years of work in the first 4 years of GDUFA I, noting that the Agency anticipated receiving only about 750 ANDAs per year under the first 5 years of the program, but instead received about 1000 ANDAs a year. Despite that fact, and the need to concentrate on rebuilding the generic drug program to be capable of meeting the negotiated GDUFA goals, the Agency has met all formal GDUFA goals to date, including reaching the ANDA backlog goal of 90% first review of all backlog applications by the end of year 5 of GDUFA ,15 months ahead of schedule (OGD is currently at 94% of backlog ANDAs and 93% of backlog Prior Approval Supplements [PAS]).
In addition, the FDA is reporting a continued and steady increase in the total regulatory actions (Approvals [AP], Complete Response Letters [CR], Refuse-to-Receive letters [RTR], and Tentative Approvals [TA]) it takes.
While OGD did have a record number of approvals and tentative approvals, it still received more ANDAs than it approved. Also, OGD continues to maintain a steady flow (more than 5400 in FY 2016) of information requests (IR) and easily correctible deficiency letters (ECD), which, according to some sponsors, have buried them! So it’s both good news and bad news and is causing many firms to internally prioritize the IRs and ECDs it receives. This is indicative of the fact that, according to Cook’s presentation in October 2012, there were 100 CRL and TA not responded to by the industry and in 2016 that number stands at about 1800 (see charts below).
OGD reports that it is also exceeding all goals on supplements and controlled correspondence (CC). Interestingly, most CC requests are targeting the Office of Pharmaceutical Quality, which appears to me to mean that there are a number of CMC issues and other related quality issues that are still unclear to industry. There have been about 5400 CCs since GDUFA started, although many have not met the OGD’s CC definition (13-18% over the last 3 years). But the large number of requests indicate that industry continues to have a lot of questions that may still impact the ability to provide a quality application for first cycle approval.
Cook spoke of the numerous Guidance documents issued including the many product-specific bioequivalence document OGD have issued. She also highlighted three important Guidance documents in development covering 1) 180-Day Exclusivity; 2) Referencing Products in ANDAs; and 3) Determining 505(b)(2) or 505(j) Pathway.
In terms of OGD’s ability to reduce the number of cycles for approval, the only data available is for a segment of the cohort year 3 applications. OGD reports that, so far, OGD has approved 22 and tentatively approved 25 of the cohort year 3 ANDAs submitted (there were 539 ANDAs submitted in cohort year three). Due to the goal dates of 15 months for action, many of the ANDA are not yet ripe (there are still 3 months where cohort year 3 ANDAs still have goal dates with goal dates that have not yet come due). However, in the first 2 months of cohort year 3 ANDAs, OGD reported early on that first cycle approval rates (including APs and TAs) was at about 14%. Now with more data available, OGD is reporting first cycle approvability rate at about 8%; however, second cycle AP/TA rates are up to 43% which is a big improvement over the 4-7 cycles most ANDAs endured in previous years.
To close, Cook recognized that meeting the new year 5 cohort goals will place more strain on the system but she noted that in fulfilling GDUFA goals (whether GDUFA cycle I or II), OGD must meet its commitments and in many cases OGD has gone beyond the negotiated commitments to improve the process to build a robust modern generic drug review process that is 1) sustainable and predictable; 2) with clear and consistent communications; 3) that demonstrates fairness across applications and applicants. Certainly not only the FDA goals — butalso the goals of industry.