Skip to main content

Comparison of Drug Approvals in Europe Versus the United States

An Analysis of Discrepancies Between Drug Products Reviewed by EMA and FDA

Therapeutic Innovation & Regulatory Science volume 48, pages 362–366 (2014)Cite this article

Abstract

Background

Regulators from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) do not always agree on interpretation of data for a drug’s safety and efficacy.

Methods and Results

The authors compared all new molecular entities approved or rejected in a 5-year period from 2007 to 2011, identified where FDA and EMA reviews resulted in different regulatory decisions, and explored potential mechanisms for the discrepancies. Thirteen entities were associated with different regulatory decisions, and 2 drugs were withdrawn from their respective markets in 2010: one from the US (Mylotarg; gemtuzumab ozogamicin) and the other in Europe (Thelin; sitaxentan sodium).

Conclusions

There are relatively few cases where FDA and EMA substantively differ with regard to product approvals and market withdrawals. It is likely that the scientific and cultural differences between FDA and EMA will continue to diminish over time, because these two agencies increasingly work together as pharmaceutical product development increasingly becomes a global endeavor.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Marc Desgrousilliers OR. Drug Development Time Is Money for Some Life-and-Death for Others. Sunnyvale, CA: Clinical Data Solution; 2012.

    Google Scholar 

  2. Tanimoto T, Tsubokura M, Mori J, Pietrek M, Ono S, Kami M. Differences in drug approval processes of 3 regulatory agencies: a case study of gemtuzumab ozogamicin. Invest New Drugs. 2013;31:473–478.

    Article  Google Scholar 

  3. Downing NS, Aminawung JA, Shah ND, Braunstein JB, Krumholz HM, Ross JS. Regulatory review of novel therapeutics: comparison of three regulatory agencies. N Engl J Med. 2012;366:2284–2293.

    CAS  Article  Google Scholar 

  4. Malinowski HJ, Westelinck A, Sato J, Ong T. Same drug, different dosing: differences in dosing for drugs approved in the United States, Europe, and Japan. J Clin Pharmacol. 2008;48:900–908.

    CAS  Article  Google Scholar 

  5. FDA. Is it true FDA is approving fewer new drugs lately? https://www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM247465.pdf. Accessed January 5, 2013.

  6. FDA. Is the US really slower than Europe at approving new drugs? https://www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM247470.pdf. Accessed January 5, 2013.

  7. European Medicines Agency. Questions and answers on recommendation for refusal of marketing application. https://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/000585/WC500017451.pdf. Accessed January 5, 2013.

  8. FDA. Fast track, breakthrough therapy, accelerated approval and priority review. https://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm. Accessed January 5, 2013.

  9. Sherrill B, Kaye JA, Sandin R, Cappelleri JC, Chen C. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology. Onco Targets Ther. 2012;5:287–296.

    Article  Google Scholar 

  10. Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31:2973–2984.

    Article  Google Scholar 

  11. Furgerson JL, Hannah WN Jr. Thompson JC. Challenge of surrogate endpoints. South Med J. 2012;105:156–160.

    Article  Google Scholar 

  12. Domanski M, Pocock S, Bernaud C, et al. Surrogate endpoints in randomized cardiovascular clinical trials. Fundam Clin Pharmacol. 2011;25:411–413.

    CAS  Article  Google Scholar 

  13. Lakshminarayana PH, Kahn JM. First do no harm: surrogate endpoints and the lesson of beta-agonists in acute lung injury. Crit Care. 2012;16:314.

    Article  Google Scholar 

  14. Wyeth Pharmaceuticals. Mylotarg briefing document prepared for the Oncologic Drugs Advisory Committee (ODAC) meeting March 12–13, 2003. https://www.fda.gov/ohrms/dockets/ac/03/briefing/3936B2_01_WyethAyerst-Mylotarg.pdf. Accessed January 5, 2013.

  15. FDA. Mylotarg (gemtuzumab ozogamicin): market withdrawal. https://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm216458.htm. Accessed January 5, 2013.

  16. Wyeth Pharmaceuticals. Mylotarg. https://labeling.pfizer.com/showlabeling.aspx?id=119. Accessed January 5, 2013.

  17. FDA. Pfizer voluntarily withdraws cancer treatment mylotarg from US market. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm216448.htm. Accessed January 5, 2013.

  18. Carroll J. The accelerated approval debate: faster FDA drug approvals may mean less efficacy data. Biotechnol Healthc. 2012;9(2):6–7.

    PubMed  PubMed Central  Google Scholar 

  19. Pfizer. Annex I: summary of product characteristics. https://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf. Accessed January 5, 2013.

  20. European Medicines Agency. Thelin (sitaxentan) to be withdrawn due to cases of unpredictable serious liver injury. https://www.ema.europa.eu/docs/en_GB/document_-library/Press_release/2010/12/WC500099707.pdf. Accessed January 5, 2013.

  21. Pfizer. Pfizer stops clinical trials of Thelin and initiates voluntary product withdrawal in the interest of patient safety. https://www.pfizer.ca/en/media_centre/news_releases/article?year=2010&article=340. Accessed January 5, 2013.

  22. Thelin: Encysive Pharmaceuticals submits new drug application for Thelin. https://www.drugs.com/nda/thelin_050525.html. Accessed January 5, 2013.

  23. Thelin: FDA issues third approvable letter for Thelin (sitaxsentan sodium). https://www.drugs.com/nda/thelin_070618.html. Accessed January 5, 2013.

  24. Thelin: FDA issues approvable letter for Thelin; one outstanding item remains. https://www.drugs.com/nda/thelin_060724.html. Accessed January 5, 2013.

  25. Thelin: FDA grants class 1 review to Encysive Pharmaceuticals’ complete response to Thelin NDA. https://www.drugs.com/nda/thelin_060615.html. Accessed January 5, 2013.

  26. Encysive Pharmaceuticals receives written response from FDA on its request for formal dispute resolution for Thelin (sitaxsentan sodium). https://www.drugs.com/nda/thelin_070906.html. Accessed January 5, 2013.

  27. FDA. FDA, European Medicines Agency launch good clinical practices initiative. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm174983.htm. Accessed January 5, 2013.

  28. FDA. SOPP 8001.6: procedures for parallel scientific advice with European Medicines Agency (EMA). https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ProceduresSOPPs/ucm061218.htm. Accessed January 5, 2013.

  29. FDA. Cooperation on drug regulation strengthened. https://www.fda.gov/InternationalPrograms/FDABeyondOurBordersForeignOffices/EuropeanUnion/EuropeanUnion/EuropeanCommission/ucm114344.htm. Accessed January 5, 2013.

  30. European Medicines Agency. ICH Topic M 4 Q: common technical document for the registration of pharmaceuticals for human use—quality. https://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002725.pdf. Accessed January 5, 2013.

  31. FDA. Interactions between the European Medicines Agency and US Food and Drug Administration September 2009–September 2010. https://www.fda.gov/downloads/InternationalPrograms/FDABeyondOurBordersForeignOffices/EuropeanUnion/EuropeanUnion/EuropeanCommission/UCM261565.pdf. Accessed January 5, 2013.

  32. Pignatti F, Gravanis I, Herold R, Vamvakas S, Jonsson B, Marty M. The European Medicines Agency: an overview of its mission, responsibilities, and recent initiatives in cancer drug regulation. Clin Cancer Res. 2011;17:5220–5225.

    Article  Google Scholar 

Download references

Author information

Affiliations

  1. Regulatory Affairs Track and Professor, Biostatistics, Yale University School of Public Health, LEPH 203, 60 College Street, New Haven, CT, 06520, USA

    Robert W. Makuch PhD & Ruizhi Shi MB, MS

Authors
  1. Robert W. Makuch PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruizhi Shi MB, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert W. Makuch PhD.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Makuch, R.W., Shi, R. Comparison of Drug Approvals in Europe Versus the United States. Ther Innov Regul Sci 48, 362–366 (2014). https://doi.org/10.1177/2168479013517103

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479013517103

Keywords

  • FDA
  • EMA
  • drug approval
  • regulatory affairs