The COVID Boom: CBER Receives More INDs in One Quarter Than The Previous 30 Combined
Executive Summary
Bubble was short-lived, but still could create workload problems for the US FDA as it navigates the end of the coronavirus pandemic.
The coronavirus pandemic attracted a historic tsunami of investigational work to the US Food and Drug Administration’s Center for Biologics Evaluation and Research, which may affect its operations even after the pandemic ends.
Interestingly, however, the dramatic spike in investigational new drug applications only lasted six months, then largely disappeared. The activity may be telling of the industry response to the pandemic and more evidence that drug developers learned relatively quickly whether COVID-19 would be a worthwhile endeavor for them.
CBER received 3,806 INDs in the third quarter of fiscal year 2020, which ended in June amid the worsening pandemic. That was 141 more than the previous 30 quarters (7.5 years), combined. Sponsors followed with another 2,769 INDs submitted in the FY 2020 fourth quarter, which ended in September, according to FDA data. (See charts below.)
But the bubble disappeared as quickly as it began. In the first quarter of FY 2021, which ended in December 2020, CBER received only 208 INDs, returning to slightly higher than the historical trend. CBER averaged 122 INDs received per quarter from the beginning of FY 2013 through the second quarter of FY 2020.
The submission bolus also coincided with a record number of IND and investigational device exemption actions. During the peak quarters, CBER issued 3,075 and 3,726 IND/IDE actions. Like the submission trend, both were abnormally high – the average number of actions per quarter from the first quarter of FY 2013 through the second quarter of FY 2020 was 240.
And like the IND submission total, IND/IDE actions also plummeted, dropping to 544 during the first quarter of FY 2021.
A CBER spokesperson told the Pink Sheet that while the center has received “a significant number of INDs related to the development of countermeasures for COVID-19,” the number of cell and gene therapy INDs also continues to grow.
“Our application review teams remain focused on their work, and we are doing everything possible to maintain continuity of operations in a very dynamic situation,” the center said. “CBER remains fully capable to continue daily activities, such as application reviews, while responding to the public health needs during the COVID-19 pandemic.”
While all the INDs will not become marketed products, the job of tracking them will require substantial resources. The upcoming prescription drug user fee reauthorization is expected to include funding to increase staffing at CBER, but that was intended to deal with the expected influx of cell and gene therapy products in the coming years. (Also see "PDUFA VII Negotiations Completed, Commitment Letter Ratification Ongoing" - Pink Sheet, 22 Mar, 2021.)
Agency staff were working around the clock and through weekends to review data and other information on potential treatments and vaccines, an unsustainable pace. (Also see "CBER’s ‘Courageous’ Coronavirus Guidance Strategy May Catch-On" - Pink Sheet, 25 Jun, 2020.)
Story continues after charts. (Be sure to click on all six tabs!)
CDER Also Sees IND Submission Increase
The Center for Drug Evaluation and Research also saw its IND submission rate increase during the pandemic, but not as dramatically as CBER.
CDER reported receiving 346 INDs during the third quarter and another 304 during the fourth quarter, totals much higher than the previous four years. Both were above the previous high of 268, as well as the average of nearly 219 received from the quarters ended in December 2015 through March 2020.
Data was not available for the quarter ended December 2020 to determine whether the submission rate fell back to normal levels.
CDER also was expecting a COVID-19-related workload boom as clinical trials read-out. (Also see "US FDA Could Be Facing Bolus Of Pandemic-Related Applications" - Pink Sheet, 16 Feb, 2021.)
The IND submission pattern in both centers seems to fit the natural pharma industry development evolution when a critical need for new treatments emerges. Many companies, researchers, and others use the opportunity to test new and repurposed therapies. But failures occur, competition increases, and companies inevitably pivot to other opportunities. (Also see "US FDA’s Coronavirus Workload Shifting Beyond Idea Stage" - Pink Sheet, 28 Jul, 2020.)
Written Response Only Meetings Spike At CDER
The COVID-19 spike did not include a rush of marketing applications at either CBER or CDER.
CBER received only 11 marketing applications during the third quarter of FY 2020, the lowest since the second quarter of FY 2015, when nine were submitted. The total increased to 20 during the fourth quarter of FY 2020 and 17 in the first quarter of FY 2021. Both were in line with the historical average of about 21 per quarter.
At CDER, the third quarter of FY 2020 constituted the bottom of a downward trend in NDA submissions that began during the first quarter that year when 29 NDAs were submitted. The total increased to 32 in the fourth quarter of FY 2020, the most recent data available.
Meeting volume, a constant headache for CDER, remained relatively steady even during the pandemic. But the number of written response only (WRO) requests spiked as the agency barred in-person sessions and adapted to virtual meeting practices. CDER reported 600 WROs scheduled during the third quarter of FY 2020 and another 569 during the fourth quarter. The previous high was 383, set in the first quarter of FY 2020.
CBER reported a substantial drop in the number of meetings held once the pandemic began. The center held 33 and then 26 meetings during the third and fourth quarters of FY 2020, respectively. The average during the 30 quarters leading up to that point was 63 per quarter.
Sponsors also cancelled 10 and 5 CBER meetings during the third and fourth quarters of FY 2020, respectively, because written feedback was provided, compared to the average leading up to the pandemic of more than 16 per quarter.
Meeting scheduling was an ongoing problem before the pandemic as FDA staff struggled to fit schedules into mandated goals. (Also see "US FDA Struggles To Meet Goals As Drug Sponsors' Meeting Requests Rise" - Pink Sheet, 16 Sep, 2019.)
The coronavirus forced meetings to become virtual, which created a different set of problems. (Also see "US FDA Shies Away From Zoom Meetings Because Of Security Concerns" - Pink Sheet, 18 Jun, 2020.)