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Drug Approval Times and User Fees

An International Perspective in a Changing World

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Abstract

On the surface it would seem that everyone — industry, patients and regulators — would be in favour of faster drug approvals. Approval times in developed countries vary significantly. One major cause of slow approval times is resource availability. In the face of government reluctance to increase funding to regulatory agencies through tax dollars, user fees (payments from industry) have been adopted in many countries. In the US, user fees were accompanied by a commitment to faster approvals, whereas in other countries there seems to have been a tacit agreement between industry and the regulator that approval times would become shorter. Information from the US, Australia and Canada shows that user fees have resulted in more rapid drug approvals and a greater percentage of new drug applications being approved. To the extent that new drugs improve health outcomes, patients have benefited, and there is some contested evidence that an increase in the use of new drugs leads to better health but the large majority of new drugs do not offer any significant therapeutic gains. At the same time as improving drug approval times, user fees have also resulted in the shunting of agency resources into the approval system and away from other regulatory functions, such as postmarketing surveillance. Furthermore, for the US Food and Drug Administration, the introduction of user fees also seems to have led to increased workloads for agency staff and lower staff moral. There is a major ongoing debate about whether or not faster approvals subsequently lead to more drug withdrawals for safety reasons. There is a body of evidence that seems to indicate that this is not the case but other metrics, such as the fate of drugs that are approved just prior to legislated deadlines, show higher rates of withdrawals for this group of drugs. Finally, many prominent doctors and academics believe that user fees have fundamentally changed the relationship between regulators, the public and industry, and there are calls in the US for the abolition of user fees.

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Notes

  1. 1In the late 1990s, the length of time a new drug application spent in the review process was just over 300 days, significantly under Health Canada’s target of 355 days, but there was an additional 350 days of waiting time before the review started.[5]

  2. 2The TPD approves and monitors prescription and nonprescription drugs derived from chemical manufacturing and medical devices; the Biologics and Genetic Therapies Directorate (BGTD) is responsible for biological and radiopharmaceutical drugs including blood and blood products, viral and bacterial vaccines, genetic therapeutic products, tissues, organs and xenografts. While responsible for different types of products both the Directorates function in an almost identical manner, and for the purposes of this article, the term TPD will be used for both

  3. 3The relevant parts of the FDA for the purposes of this paper are the Center for Drug Evaluation and Research, which regulates drugs derived from chemical manufacturing, and the Center for Biologics Evaluation and Research, which regulates blood and blood products, vaccines and allergenic products and protein-based drugs

  4. 4The pharmaceutical industry also had a significant role to play in the long approval times. In many cases, the initial files sent to the FDA had major inadequacies and companies took prolonged periods of time to respond to FDA queries.[8]

  5. 5The TGA is the Australian equivalent to the FDA and the TPD

  6. 6The Medicines Control Agency is now the Medicines and Healthcare products Regulatory Agency (MHRA)

  7. 7‘ Priority’ review drugs are those thought to have the potential for significant therapeutic gains

  8. 8Olson[18] makes the point that the increase in hospitalizations and deaths due to ADRs needs to be balanced against the benefits of quicker access to new drugs

References

  1. Rx&D. Improving health through innovation: a new deal for Canadians [online]. Available from URL: http://www.innovationstrategy.gc.ca/gol/innovation/site.nsf/vDownload/SectorReports_e/$file/Pharmaceuticals-e.pdf 2002 [Accessed 2007 Dec 5]

    Google Scholar 

  2. Rawson NSB. Timeliness of review and approval of new drugs in Canada from 1999 through 2001: is progress being made? Clin Ther 2003; 25: 1230–47

    Article  PubMed  Google Scholar 

  3. Anderson C, McAuslane N, Walker S. The impact of the changing regulatory environment on review times. R&D Briefing No. 35. CMR International [online]. Available from URL: http://www.cmr.org/pdf/r_d35.pdf [Accessed 2007 Dec 5]

    Google Scholar 

  4. Rawson NSB. Human resources for the approval of new drugs in Canada, Australia, Sweden, the United Kingdom and the United States. Can J Clin Pharmacol 2002; 9: 73–8

    PubMed  Google Scholar 

  5. Zelenay Jr JL. The prescription drug user fee act: is a faster Food and Drug Administration always a better Food and Drug Administration? Food Drug Law J 2005; 60: 261–338

    PubMed  Google Scholar 

  6. Peterson RG. Response to commentary. Pharmacoepidemiol Drug Saf 2002; 11: 341–2

    Article  Google Scholar 

  7. Hilts PJ. Protecting America’s health: the FDA, business, and one hundred years of regulation. New York: Alfred A. Knopf, 2003

    Google Scholar 

  8. US Food and Drug Administration. FY 2003 PDUFA financial report. Washington, DC: Department of Health and Human Services, 2004 [online]. Available from URL: http://www.fda.gov/oc/pdufa/finreport2003/financial-fy2003.html [Accessed 2007 Dec 5]

    Google Scholar 

  9. US Food and Drug Administration. Effect of user fees on drug approval times, withdrawals, and other agency activities. Washington, DC: US General Accounting Office, 2002 Sep. Report No.: GAO-02-958 [online]. Available from URL: http://www.gao.gov/new.items/d02958.pdf [Accessed 2007 Dec 5]

    Google Scholar 

  10. US Food and Drug Administration. FY 2005 PDUFA financial report. Washington, DC: Department of Health and Human Services, 2006 [online]. Available from URL: http://www.fda.gov/oc/pdufa/finreport2005/PDUFA05finrpt.html [Accessed 2007 Dec 5]

    Google Scholar 

  11. Lexchin J. Relationship between pharmaceutical company user fees and drug approvals in Canada and Australia: a hypothesis-generating study. Annals Pharmacother 2006; 40: 2216–22

    Article  Google Scholar 

  12. KPMG Consulting LP. Report volume 1: review of the Therapeutic Products Programme cost recovery initiative. Ottawa (ON): 2000 June 16. Executive summary [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/crsummary_rcresume_e.pdf [Accessed 2008 Jan 8]

    Google Scholar 

  13. Australian National Audit Office. Drug evaluation by the Therapeutic Goods Administration: Department of Health and Family Services [Audit report no. 8 1996–97]. Canberra (ACT): AGPS, 1996

    Google Scholar 

  14. Lofgren H, de Boer R. Pharmaceuticals in Australia: developments in regulation and governance. Soc Sci Med 2004; 58: 2397–407

    Article  PubMed  Google Scholar 

  15. Abraham J. Science, politics and the pharmaceutical industry: controversy and bias in drug regulation. London: UCL Press Ltd, 1995

    Google Scholar 

  16. Health Canada. Cost recovery framework: international comparison of fees and service standards for human drugs [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/pubs/finance/2007-crf-crc-drug-hum-med/index_e.html [Accessed 2007 Dec 5]

    Google Scholar 

  17. Carpenter D, Chernew M, Smith DG, et al. Approval times for new drugs: does the source of funding for FDA staff matter? Health Aff (Millwood) 2003; Suppl. W3: 618–24

    Google Scholar 

  18. Olson MK. Pharmaceutical policy change and the safety of new drugs. J Law Econ 2002; 45: 615–42

    Article  Google Scholar 

  19. Olson MK. Explaining reductions in FDA drug regulatory times: PDUFA matters. Health Aff (Millwood) 2004; Suppl. W4: S1–2

    Google Scholar 

  20. US Food and Drug Administration. CDER approval times for priority and standard NDAs and BLAs, calendar years 1993–2006 [online]. Available from URL: http://www.fda.gov/cder/rdmt/NDAapps93-06.htm [Accessed 2007 Nov 6]

    Google Scholar 

  21. US Food and Drug Administration. CDER approval times for priority and standard NMEs and new BLAs, calendar years 1993–2006 [online]. Available from URL: http://www.fda.gov/cder/rdmt/NMEapps93-06.htm [Accessed 2007 Aug 10]

    Google Scholar 

  22. US Food and Drug Administration Office of Planning. FY 2006: performance report to the president and the congress for the prescription drug user fee act [online]. Available from URL: http://www.fda.gov/ope/pdufa/report2006/default.htm [Accessed 2007 Dec 5]

    Google Scholar 

  23. US Food and Drug Administration. FY 2000 performance report to Congress for the Prescription Drug User Fee Act of 1992 [online]. Available from URL: http://www.fda.gov/ope/pdufa/report2000/default.htm [Accessed 2007 Dec 5]

    Google Scholar 

  24. Drugs Directorate. Strategic framework for the drugs programme 1996–1999. Ottawa (ON): Health Canada, Health Protection Branch, 1996 May

    Google Scholar 

  25. Australian National Audit Office. Drug evaluation by the Therapeutic Goods Administration: follow-up audit [Audit report no. 2: 2000–2001]. Department of Health and Aged Care, Therapeutic Goods Administration [online]. Available from URL: http://www.anao.gov.au/uploads/documents/2000-01_Audit_Re-port_2.pdf [Accessed 2007 Dec 5]

    Google Scholar 

  26. Lichtenberg FR. Are the benefits of newer drugs worth their cost? Evidence from the 1996 MEPS. Health Aff 2001; 20 (5): 241–51

    Article  CAS  Google Scholar 

  27. Lichtenberg FR. Benefits and costs of newer drugs: an update. Cambridge (MA): National Bureau of Economic Research, 2002

    Book  Google Scholar 

  28. Patented Medicine Prices Review Board. Annual report 2004. Ottawa (ON): Patented Medicine Prices Review Board, 2005 [online]. Available from URL: http://www.pmprb-cepmb.gc.ca/english/view.asp?x=436 [Accessed 2007 Dec 5]

    Google Scholar 

  29. A look back at pharmaceuticals in 2006: aggressive advertising cannot hide the absence of therapeutic advances. Prescrire Int 2007; 16 (88): 80–6

    Google Scholar 

  30. Garattini S, Bertele V. Efficacy, safety, and cost of new anticancer drugs. BMJ 2002; 325: 269–71

    Article  PubMed  Google Scholar 

  31. Joppi R, Bertele V, Garattini S. Disappointing biotech. BMJ 2005; 331: 895–7

    Article  PubMed  Google Scholar 

  32. Lichtenberg FR. New drugs and lower costs. Am J Health System Pharm 2002; 59: 1894–5

    Google Scholar 

  33. Mintzes B, Lexchin J. Do higher drug costs lead to better health? Can J Clin Pharmacol 2005; 12: e10–21

    Google Scholar 

  34. Zhang Y, Soumerai S. Do newer prescription drugs pay for themselves? A reassessment of the evidence. Health Aff 2007; 26 (3): 880–6

    Article  Google Scholar 

  35. Miller GE, Moeller JF, Stafford RS. New cardiovascular drugs: patterns of use and association with non-drug health expenditures. Inquiry 2006; 42 (4): 397–412

    Article  Google Scholar 

  36. Lichtenberg FR. On “new cardiovascular drugs: patterns of use and association with non-drug health expenditures”. Inquiry 2006; 43: 80–2

    PubMed  Google Scholar 

  37. Lichtenberg FR. Effects of new drugs on overall health spending: Frank Lichtenberg responds. Health Aff 2007; 26 (3): 887–90

    Article  Google Scholar 

  38. Lurie P, Wolfe SM. FDA medical officers report lower standards permit dangerous drug approvals. Washington, DC: Public Citizen, 1998 [online]. Available from URL: http://www.citizen.org/publications/release.cfm?ID=7104 [Accessed 2007 Dec 6]

    Google Scholar 

  39. Office of Inspector General. FDA’s review process for new drug applications: a management review. Washington, DC: Department of Health and Human Services, 2003 Mar [online]. Available from URL: http://oig.hhs.gov/oei/re-ports/oei-01-01-00590.pdf [Accessed 2007 Dec 6]

    Google Scholar 

  40. Okie S. What ails the FDA? N Engl J Med 2005; 352 (11): 1063–6

    Article  PubMed  CAS  Google Scholar 

  41. Abraham J, Lewis G. Europeanization of medicines regulatioin. In: Abraham J, Smith HL, editors. Regulation of the pharmaceutical industry. Basingstoke: Palgrave Macmillan, 2003: 42–81

    Chapter  Google Scholar 

  42. House of Commons Health Committee. The influence of the pharmaceutical industry: fourth report of session 2004–05. volume 1. Report no. HC 42-1 [online]. Available from URL: http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/42/42.pdf [Accessed 2007 Dec 5]

  43. US General Accounting Office. FDA drug review: postapproval risks 1976–85. Report no. GAO/PEMD-90-15 [online]. Available from URL: http://www.mindfully.org/Health/FDA-Postapproval-RisksGAOApr1990.htm [Accessed 2007 Dec 5]

    Google Scholar 

  44. Abraham J, Davis C. A comparative analysis of drug safety withdrawals in the UK and the US (1971–1992): implications for current regulatory thinking and policy. Soc Sci Med 2005; 61: 881–92

    Article  PubMed  Google Scholar 

  45. Health Canada. Advisories warnings and recalls: for health professionals [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2007/index_e.html [Accessed 2007 Aug 10]

    Google Scholar 

  46. Health Canada. Drug submission performance reports: annual reports. 2006 [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/docs/perform-rendement/ar-ra/index_e.html [Accessed 2007 Aug 10]

    Google Scholar 

  47. Lexchin J. Drug withdrawals from the Canadian market for safety reasons, 1963–2004. CMAJ 2005; 172: 765–7

    Article  PubMed  Google Scholar 

  48. Friedman MA, Woodcock J, Lumpkin MM, et al. The safety of newly approved medicines: do recent market removals mean there is a problem? JAMA 1999; 281: 1728–34

    Article  PubMed  CAS  Google Scholar 

  49. Drug safety withdrawals in the US not linked to speed of FDA approval. Tufts Center Study Drug Dev 2005; 7 (5): 1–4

    Google Scholar 

  50. Berndt ER, Gottschalk AHB, Philipson TJ, et al. Industry funding of the FDA: effects of PDUFA on approval times and withdrawal rates. Nature Rev Drug Disc 2005; 4: 545–54

    Article  CAS  Google Scholar 

  51. Center for Drug Evaluation and Research, US Department of Health and Human Services. 2005 Report to the nation: improving public health through human drugs [online]. Available from URL: http://www.fda.gov/cder/reports/rtn/2005/rtn2005.pdf [Accessed 2007 Dec 6]

    Google Scholar 

  52. Carpenter D, Bowers J, Grimmer J, et al. Deadline effects in regulatory drug review: a methodological and empirical analysis. Version 2.1, 2007 [online]. Available from URL: http://www.defendingscience.org/newsroom/upload/Carpenter_FDA_Deadlines-2.pdf [Accessed 2007 Dec 6]

    Google Scholar 

  53. Hunt MI. Prescription drugs and intellectual property protection: finding the right balance between access and innovation. Washington, DC: National Institute for Health Care Management, 2000

    Google Scholar 

  54. Duckwitz N, Yuan Y. Doctors & DTC. Pharm Exec 2002; 22 (9): 114–24 [online]. Available from URL: http://www.pharmexec.com/pharmexec/article/articleDetail.jsp?id=29973 [Accessed 2007 Nov 7]

    Google Scholar 

  55. IMS Health. Leading 10 products by US DTC spend, 2000 [online]. Available from URL: http://www.uaccimshealth.com/ims/portal/front/articleC/0,2787,6599_40054629_1004776,00.html [Accessed 2008 Jan 8]

    Google Scholar 

  56. CBC-TV, Disclosure. Targeting doctors. Graph: top 50 drugs by promotional dollars. CBC, 2002 [online]. Available from URL: http://www.cbc.ca/disclo-sure/archives/0103_pharm/resources.html [Accessed 2006 May 15]

    Google Scholar 

  57. Mamdani M, Juurlink DN, Kopp A, et al. Gastrointestinal bleeding after the introduction of COX 2 inhibitors: ecological study. BMJ 2004; 328: 1415–6

    Article  PubMed  Google Scholar 

  58. Christensen S, Riis A, Nørgaard M, et al. Introduction of newer selective cyclooxygenase-2 inhibitors and rates of hospitalization with bleeding and perforated peptic ulcer. Aliment Pharmacol Ther 2007; 25: 907–12 [online]. Available from URL: http://pt.wkhealth.com/pt/re/alpt/pdfhandler.00001716-200704080-00006.pdf

    Article  PubMed  CAS  Google Scholar 

  59. Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002; 287: 2215–20

    Article  PubMed  Google Scholar 

  60. Stigler G. The theory of economic regulation. Bell J Econ Manag Sci 1971; 2: 2–21

    Article  Google Scholar 

  61. Lawson GW. Impact of user fees (i.e. drug industry money) on changes within the FDA. University of La Verne, School of Public Management, 2005 [online]. Available from URL: http://www.fdastudy.com [Accessed 2005 Mar 26]

    Google Scholar 

  62. Rx&D. Improving health through innovation: a new deal for Canadians. Ottawa (ON): Canada’s Research-Based Pharmaceutical Companies, 2002 Sep [online]. Available from URL: http://www.innovationstrategy.gc.ca/gol/innovation/site.nsf/vDownload/SectorReports_e/$file/Pharmaceuticals-e.pdf [Accessed 2007 Dec 6]

    Google Scholar 

  63. Therapeutic Products Directorate. Business transformation progress report 2004–2005. Ottawa (ON): Health Canada, 2004 [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/docs/bt_rep_to_rap_2004_05_e.html [Accessed 2007 Dec 6]

    Google Scholar 

  64. Health Canada. Improving Canada’s regulatory process for therapeutic products: building the action plan. Public Policy Forum: multistakeholder consultation. 2003 Nov 2–3.

    Google Scholar 

  65. Baume P. A question of balance: report on the future of drug evaluation in Australia. Canberra: AGPS, 1991

    Google Scholar 

  66. APMA annual report 2001 [online]. Available from URL: http://www.medicinesaustralia.com.au/ [Accessed 2005 Oct 6]

  67. Griffiths K. The interview: drug tsar who took on the system. David Graham, FDA whistleblower. The Independent 2005 Feb 12 [online]. Available from URL: http://news.independent.co.uk/business/analysis_and_features/article10689.ece [Accessed 2007 Dec 6]

    Google Scholar 

  68. Hennessy S, Strom BL. PDUFA reauthorization: drug safety’s golden moment of opportunity? N Engl J Med 2007; 356: 1703–4

    Article  PubMed  CAS  Google Scholar 

  69. Angell M, Avorn J, Bingham E, et al. An open letter to: Chairman Edward Kennedy and Senator Mike Enzi, Chairman John Dingell and Representative Joe Barton [online]. Available from URL: http://www.defendingscience.org/newsroom/upload/PDUFA_Open_Letter.pdf [Accessed 2007 Aug 11]

    Google Scholar 

  70. McClellan M. Drug safety reform at the FDA: pendulum swing or systematic improvement? N Engl J Med 2007; 356: 1700–2

    Article  PubMed  CAS  Google Scholar 

  71. Food and drug administration amendments act of 2007, Public Law HR 3580. 110th Session of United States Congress, 2007

    Google Scholar 

  72. Goozner M. The failure of FDA reform. 2007 Oct [online]. Available from URL: http://commentisfree.guardian.co.uk/merrill_goozner/2007/10/fda_reform.html.printer.friendly [Accessed 2007 Oct 2]

    Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The author has been retained as an expert by Apotex Inc. in a court case against Pfizer over the introduction of a generic form of atorvastatin into Canada.

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  1. School of Health Policy and Management, Faculty of Health, York University, 121 Walmer Rd, Toronto, Ontario, M5R 2X8, Canada

    Joel Lexchin

  2. Emergency Department, University Health Network, Toronto, Ontario, Canada

    Joel Lexchin

  3. Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada

    Joel Lexchin

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Lexchin, J. Drug Approval Times and User Fees. Pharm Med 22, 1–11 (2008). https://doi.org/10.1007/BF03256677

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