FAST-TRACKING DRUG APPROVALS: A SYSTEMATIC REVIEW OF THE US FDA'S EXPEDITED REGULATORY PATHWAYS
DOI:
https://doi.org/10.22159/ijap.2025v17i5.54440Keywords:
FDA, Expedited approval, Priority review, Orphan drug designation, Fast track, Breakthrough therapy, Accelerated approvalAbstract
The current review explores the utilization and impact of the United States Food and Drug Administration’s (US-FDA) accelerated drug approval pathways over the past decade (2014–2024). Specifically, it evaluates five key programs: Orphan Drug Designation, Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval. The primary aim is to assess how these expedited pathways influence drug development timelines and overall approval success rates. A comprehensive literature search was conducted using databases such as PubMed, Scopus, Web of Science, and Google Scholar. The search yielded 200 articles, of which 110 met the inclusion criteria. From these, 25 key studies were selected for detailed analysis. The findings indicate that Priority Review accounted for the highest number of drug approvals (367 approvals, 55%), followed by Orphan Drug Designation (279 approvals, 42%) and Fast Track (215 approvals, 32%). Breakthrough Therapy and Accelerated Approval contributed to 124 (19%) and 103 (15%) approvals, respectively. These programs have significantly accelerated the availability of essential treatments, particularly in oncology and rare diseases. However, challenges persist. The reliance on surrogate endpoints raises concerns about long-term efficacy, and the need for rigorous post-marketing surveillance remains critical to ensure safety and therapeutic value. In conclusion, the increasing adoption of these accelerated pathways underscores their growing importance in meeting urgent medical needs. While they offer promising benefits in terms of faster access to life-saving therapies, a balanced approach that ensures thorough evaluation and long-term monitoring is essential for sustained public health outcomes.
References
1. Phillips AT, Desai NR, Krumholz HM, Zou CX, Miller JE, Ross JS. Association of the FDA amendment act with trial registration publication and outcome reporting. Trials. 2017;18(1):333. doi: 10.1186/s13063-017-2068-3, PMID 28720112.
2. Miller JE, Wilenzick M, Ritcey N, Ross JS, Mello MM. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies. BMJ Open. 2017;7(12):e017917. doi: 10.1136/bmjopen-2017-017917, PMID 29208616.
3. Wolford JE, Tewari KS. US FDA oncology drug approvals in 2014. Future Oncol. 2015;11(13):1931-45. doi: 10.2217/fon.15.106, PMID 26039742.
4. Vaggelas A, Seimetz D. Expediting drug development: FDA’s new regenerative medicine advanced therapy designation. Ther Innov Regul Sci. 2019;53(3):364-73. doi: 10.1177/2168479018779373, PMID 29895180.
5. US Food and Drug Administration. Novel drug approvals for 2018. In: Silver Spring, MD: FDA; 2018 Jul 12. Available from: https://www.fda.gov/drugs. [Last accessed on 11 Dec 2018].
6. Batta A, Kalra BS, Khirasaria R. Trends in FDA drug approvals over last 2 decades: an observational study. J Fam Med Prim Care. 2020;9(1):105-14. doi: 10.4103/jfmpc.jfmpc_578_19, PMID 32110574.
7. Michaeli DT, Michaeli T, Albers S, Boch T, Michaeli JC. Special FDA designations for drug development: orphan fast track accelerated approval priority review and breakthrough therapy. Eur J Health Econ. 2024;25(6):979-97. doi: 10.1007/s10198-023-01639-x, PMID 37962724.
8. Puthumana J, Miller JE, Kim J, Ross JS. Availability of investigational medicines through the US food and drug administration’s expanded access and compassionate use programs. JAMA Netw Open. 2018;1(2):e180283. doi: 10.1001/jamanetworkopen.2018.0283, PMID 30646072.
9. Williams CT. Food and drug administration drug approval process: a history and overview. Nurs Clin North Am. 2016;51(1):1-11. doi: 10.1016/j.cnur.2015.10.007, PMID 26897420.
10. Kepplinger EE. FDA’s expedited approval mechanisms for new drug products. Biotechnol Law Rep. 2015;34(1):15-37. doi: 10.1089/blr.2015.9999, PMID 25713472.
11. G De La Torre B, Albericio F. The pharmaceutical industry in 2018. An analysis of FDA drug approvals from the perspective of molecules. Molecules. 2019;24(4):809. doi: 10.3390/molecules24040809, PMID 30813407.
12. Kepplinger EE. FDA’s expedited approval mechanisms for new drug products. Biotechnol Law Rep. 2015;34(1):15-37. doi: 10.1089/blr.2015.9999, PMID 25713472.
13. Cross S, Rho Y, Reddy H, Pepperrell T, Rodgers F, Osborne R. Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine? BMJ Glob Health. 2021;6(12):e007321. doi: 10.1136/bmjgh-2021-007321, PMID 34937701.
14. Cama J, Leszczynski R, Tang PK, Khalid A, Lok V, Dowson CG. To push or to pull? In a post-COVID world supporting and incentivizing antimicrobial drug development must become a governmental priority. ACS Infect Dis. 2021;7(8):2029-42. doi: 10.1021/acsinfecdis.0c00681, PMID 33606496.
15. Ardal C, Rottingen JA, Opalska A, Van Hengel AJ, Larsen J. Pull incentives for antibacterial drug development: an analysis by the transatlantic task force on antimicrobial resistance. Clin Infect Dis. 2017;65(8):1378-82. doi: 10.1093/cid/cix526, PMID 29017240.
16. Alexander GC, Knopman DS, Emerson SS, Ovbiagele B, Kryscio RJ, Perlmutter JS. Revisiting FDA approval of aducanumab. N Engl J Med. 2021;385(9):769-71. doi: 10.1056/NEJMp2110468, PMID 34320282.
17. Mandl KD, Kohane IS. Data citizenship under the 21st Century Cures Act. N Engl J Med. 2020;382(19):1781-3. doi: 10.1056/NEJMp1917640, PMID 32160449.
18. Hudson KL, Collins FS. The 21st century cures act a view from the NIH. N Engl J Med. 2017;376(2):111-3. doi: 10.1056/NEJMp1615745, PMID 27959585.
19. US Food and Drug Administration. Development and approval process. Silver Spring, MD: FDA Drugs; 2021. Available from: https://www.fda.gov/drugs/development-approval-process-drugs. [Last accessed on 13 Dec 2021].
20. Ballreich J, Bennet C, Moore TJ, Alexander GC. Medicare expenditures of atezolizumab for a withdrawn accelerated approved indication. JAMA Oncol. 2021;7(11):1720-1. doi: 10.1001/jamaoncol.2021.4757, PMID 34554196.
21. Mullard A. FDA drug approvals. Nat Rev Drug Discov. 2020;20:85-90.
22. Puthumana J, Wallach JD, Ross JS. Clinical trial evidence supporting FDA approval of drugs granted breakthrough therapy designation. JAMA. 2018;320(3):301-3. doi: 10.1001/jama.2018.7619, PMID 30027239.
23. Brown DG, Wobst HJ. A decade of FDA-approved drugs (2010-2019): trends and future directions. J Med Chem. 2021;64(5):2312-38. doi: 10.1021/acs.jmedchem.0c01516, PMID 33617254.
24. Kwok M, Foster T, Steinberg M. Expedited programs for serious conditions: an update on breakthrough therapy designation. Clin Ther. 2015;37(9):2104-20. doi: 10.1016/j.clinthera.2015.07.011, PMID 26297571.
25. Ribeiro TB, Buss L, Wayant C, Nobre MR. Comparison of FDA accelerated vs regular pathway approvals for lung cancer treatments between 2006 and 2018. PLOS One. 2020;15(7):e0236345. doi: 10.1371/journal.pone.0236345, PMID 32706800.
26. Michaeli DT, Michaeli T. Breakthrough therapy cancer drugs and indications with FDA approval: development time innovation trials clinical benefit, epidemiology and price. J Natl Compr Canc Netw. 2024;22(4):e237110. doi: 10.6004/jnccn.2023.7110, PMID 38648855.
27. Shepshelovich D, Tibau A, Goldvaser H, Molto C, Ocana A, Seruga B. Postmarketing modifications of drug labels for cancer drugs approved by the US food and Drug Administration between 2006 and 2016 with and without supporting randomized controlled trials. J Clin Oncol. 2018;36(18):1798-804. doi: 10.1200/JCO.2017.77.5593, PMID 29641296.
28. Liberti L, Bujar M, Breckenridge A, Hoekman J, McAuslane N, Stolk P. FDA facilitated regulatory pathways: visualizing their characteristics, development and authorization timelines. Front Pharmacol. 2017 Apr 3;8:161. doi: 10.3389/fphar.2017.00161, PMID 28420989.
29. Franco P, Jain R, Rosenkrands Lange E, Hey C, Koban MU. Regulatory pathways supporting expedited drug development and approval in ICH member countries. Ther Innov Regul Sci. 2023;57(3):484-514. doi: 10.1007/s43441-022-00480-3, PMID 36463352.
30. Hotaki LT, Shrestha A, Bennett MP, Valdes IL, Lee SH, Wang Y. Comparative expedited regulatory programs of U.S food & Drug Administration and Project Orbis Partners. Ther Innov Regul Sci. 2023;57(4):875-85. doi: 10.1007/s43441-023-00522-4, PMID 37072651.
31. Alqahtani S, Seoane Vazquez E, Rodriguez Monguio R, Eguale T. Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals? Pharmacoepidemiol Drug Saf. 2015;24(7):709-15. doi: 10.1002/pds.3793, PMID 26013294.
32. Darrow JJ, Avorn J, Kesselheim AS. FDA approval and regulation of pharmaceuticals, 1983-2018. JAMA. 2020;323(2):164-76. doi: 10.1001/jama.2019.20288, PMID 31935033.
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Copyright (c) 2025 Preetham NS, Sarath Mundra, Neil Messiah Lopes, Akhilesh Dubey
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