Generic drug data show steady year-over-year trends in first-cycle approvals, refuse-to-receive decisions

New data reported by the FDA’s Office of Generic Drugs show consistency in the number of generic applications the FDA refused to receive and the number of first cycle approvals, though the data do show some important and subtle changes, too.

Quick background:

• AgencyIQ regularly analyzes monthly data released by the FDA about generic drug approvals. Most recently, we analyzed 2021 fiscal year totals for both full and tentative Abbreviated New Drug Application (ANDA) approvals and submissions.
• As previously noted, FY2021 approval numbers were the lowest since 2016. In FY2021 the agency made a total of 679 ANDA approvals in full as well as another 157 tentative approvals. This is a slight drop from FY2020, in which it granted 737 full approvals and 172 tentative approvals. However, it is substantially lower than the agency’s peak in FY2019 when it granted 935 full approvals and 236 tentative approvals.
• This is likely due to a decline in submissions. Submissions fell for the fourth year in a row with only 808 generic applications sent to the agency during FY2021. This is the lowest total since 539 were received in FY2015 and represents a 38% decrease since the agency’s peak submission year in FY2017 when 1,306 ANDAs were received.

The agency has now published full data for FY2021, including the number of applications the FDA refused, the number withdrawn and the number of first-cycle approvals.

• Annual data for Refuse-to-Receive (RTR) applications and first cycle approvals stayed consistent. In FY2021 just 46 ANDA submissions were refused by the agency. Such rejections typically happen if an application is incomplete or otherwise clearly deficient. This number is consistent with totals from FY2020 (42 RTRs) and FY2019 (52 RTRs). However, this does represent a substantial improvement relative to recent history. For example, the average number of annual RTRs between FY2013 and FY2018 was 179. This likely demonstrates an improved understanding of the ANDA process and requirements over time, especially following the second reauthorization of the Generic Drug User Fee Act in 2017.
• Complete Responses (CRs) appear to be decreasing as part of a multi-year trend. In FY2018, the FDA issued 2638 Complete Response Letters, which indicate that an application cannot be approved in its current form, up substantially from 1603 the year before. However, every year since the FDA has issued fewer CRLs. In FY2021, FDA issued just 1851 CRLs, down from 2010 in FY2020 and 2310 in FY2019.
• The number of first-cycle approvals was also flat compared to last year. In FY2021, 121 ANDAs were approved during their first cycle of review, of which 19 were tentative first-cycle approvals. This compares to 122 first cycle approvals in FY2020, with 16 being tentative. However, first-cycle approvals represent a higher total proportion of FY2021 approvals than FY2020 approvals.
• AgencyIQ also reviewed data on the use of Information Requests (IRs) and Discipline Review Letters (DRLs). A DRL is meant to convey “early thoughts on possible deficiencies found” during a review by a discipline review team, while an IR letter requests additional information to help proceed with a review or clarify something. While the FDA has only published data on these documents for the past four fiscal years, there are not yet any clear trends in their use. IRs show the most consistency, with FDA issuing between 4150 and 4500 per year. DRLs have a wider range, with FDA issuing only 2048 DRLs in FY2018 compared to almost 3000 in FY2019.
• The one exception is IRs for original ANDAs compared to supplements. Over the last four years the number of IRs issued for original ANDAs has decreased significantly as the number of IRs for supplements has increased. In FY2018, 3292 IRs were for original applications and 1160 were for supplements. By 2020 these proportions shifted with 2480 IRs for original applications and 1833 for supplements.
• With GDUFA III upcoming, these trends are subject to change. The FDA’s proposal focuses on improving efficiencies, increasing touchpoints between the agency and sponsors and clarifying the path to market for complex generics, which have historically been more difficult to develop and get approved. These changes could increase the number of IRs and DRLs, improve first-cycle approvals, and potentially increase the total number of approvals or submissions after a recent low. [ Read our analysis of the GDUFA III Commitment Letter here.]

To contact the author of this analysis, please email Lily Rosenfield.
To contact the editor of this analysis, please email Alec Gaffney.

Key Documents and Dates

Generic Drugs Program Activities Report – Monthly Performance