As many others experienced with the COVID-19 pandemic, the United States Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research (CDER) dealt with several challenges, including work and logistic challenges.
According to a recent report released by CDER, the agency was able to maintain most of its user fee goals, its performance in moving original biosimilar applications did not keep pace.
PDUFA and GDUFA
For applications under the Prescription Drug User Fee Act (PDUFA), CDER met its target date at least 93% of the time on original applications, at least 95% of the time on efficacy supplements, and at least 97% of the time on manufacturing supplements. Applications submitted under the Generic Drug User Fee Amendments (GDUFA), CDER met its target dates at least 89% of the time on original applications, at least 94% of the time on original applications with imminent approval, at least 95% of the time on prior approval supplements, and at least 97% of the time on PAS with imminent approval. At the time the report was published, CDER did not have figures for FY2021 Q2 (January 1, 2021 – March 31, 2021) on the percentage of original applications with imminent approval or PAS with imminent approval.
By reaching the 90% mark for most of its target dates, FDA has met the goal it typically sets to meet its user fee program commitments, despite the COVID-19 pandemic.
BsUFA
Interestingly, all types of Biosimilar User Fee Act (BsUFA) applications were handled on time 100% of the time in the third quarter of FY20 (April 1, 2020 through June 30, 2020). For supplements with clinical data, the perfect score was maintained through all quarters in the reporting period. However, manufacturing supplements fell to 95% and 94% on-time handling in the last two quarters of reporting.
However, in the fourth quarter of FY 2020 and first quarter of FY 2021, CDER was only able to meet the target date 75% of the time and 67%, respectively.
ANDA Originals and ANDA/NDA/BLA Manufacturing Supplements
In the third quarter of FY20, CDER approved 17 abbreviated new drug applications (ANDAs) and 314 manufacturing supplements. ANDA original application approvals held steady until Q2 2021, when it dropped off to 8 approvals. Supplement Approvals fell a bit, to 277 in Q4 of FY20, 149 in Q1 of FY21, and 176 in Q2 of FY21.
Inspections
CDER noted that it continued to use a risk-based approach to identify the need for pre-approval inspections (PAIs), as not all application reviews actually warrant pre-approval inspections (historically around 20%). CDER also continued to conduct “mission critical inspections of domestic and foreign manufacturing facilities” to ensure compliance with CDER’s high standards. Similarly, “mission critical” pre-approval and for-cause assignments under the Bioresearch Monitoring program are considered for on-site inspection on a case-by-case basis.
CDER said that it had been using alternative approaches to inspections because of travel limitations, quarantine and social distancing requirements or lockdowns, including:
- Reviewing the inspection history of facilities to assess feasibility of relying on records or trusted partner inspections
- Using information shared by trusted foreign regulatory partners
- Requesting records directly from facilities in lieu of drug and biological product inspections
- Performing remote interactive evaluations in which we remotely evaluate livestreamed video of facility operations and engage in other remote, live interactions with facility operators.
CDER completed facility assessments to meet necessary dates by reducing the need to conduct PAIs 58% of the time in FY2020 Q3, 64% of the time in FY2020 Q4, 56% of the time in FY2021 Q1, and 48% of the time in FY2021 Q2.
New Molecular Entities
CDER also approved a record-breaking 14 new molecular entities (NMEs) in the first quarter of 2021, up from 11 during Q1 of 2020. When considered with the 53 NMEs approved in FY 2020, the approval rate of novel drugs remained constant throughout the COVID-19 pandemic.
Center for Biologics Evaluation and Research (CBER)
Unfortunately, the high pace of new drug approvals achieved CDER was not replicated by the CBER, largely because that agency had to pivot to expedited review of, and issuing emergency use authorizations for, COVID-19 vaccines and therapies. CBER approved only one novel drug in the first quarter of 2021, down from three in 2020’s first quarter; and approved a total of only six novel drugs in 2020, down from 22 the year before.