OBJECTIVES: U.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceuticals. We characterized all new molecular entities (NMEs), therapeutic biologics, and gene and cell therapies approved by the FDA during 1980-2022 in the context of these laws and regulations.

METHODS: Retrospective cohort study using publicly available data for all NMEs, therapeutic biologics, and gene and cell therapies approved by the U.S. FDA from 1980 to 2022. Descriptive analyisis was performed.

RESULTS: Between 1980-2022, the FDA approved 1,355 new drugs, including 1,103 NMEs, 235 therapeutic biologics, and 17 gene and cell therapies. The average annual drug approvals increased from 23.1 in the period 1980-Prescription Drug User Fee Act (PDUFA, 1992) to 45.0 in the period Food and Drug Administration Safety and Innovation Act (FDASIA, 2012)-2022. The FDA approved 51.3% of drugs using priority, 11.4% accelerated approval, 26.2% fast-track designation, and 24.7% breakthrough therapy designation. Orphan designations were given to 36.8% of the drugs. Antineoplastic and immunomodulating agents led in approvals and in receiving expedited designations. The median FDA review time decreased from 26.6 (interquartile range 23.6) months in pre-PDUFA period to 9.9 (4.1) months in the FDASIA-2022 period.

CONCLUSIONS: During the period 1980-2022, there was an increase in the approval of new drugs. A significant proportion of the newly approved drugs were approved through designations and expedited review procedures, which do not require the demonstration of addressing unmet medical needs or providing superior patient benefits compared to existing marketed alternatives. Throughout the study period, the legislative objective of bringing more drugs to the US market more quickly has been accomplished; however, the regulatory basis for evidence for approval has lessened. Whether the new drugs approved via expedited pathways have enhanced patient outcomes or provided therapeutic advantages for unmet medical needs warrants further research.