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Pre-market development times for biologic versus small-molecule drugs

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Fig. 1: Cumulative distribution of time from first patent filing (Patent Priority Date) to FDA approval for biologics versus small molecules.


  1. Mossinghoff, G. J. Food Drug Law J. 54, 187–194 (1999).

    CAS  PubMed  Google Scholar 

  2. Dunn, M. K. Nat. Rev. Drug Discov. 10, 487–488 (2011).

    Article  CAS  Google Scholar 

  3. Pew Charitable Trusts. Policy proposal: reducing the exclusivity period for biological products. (2017).

  4. Husser, A. Will USMCA affect Canada’s drug prices? Depends on what happens next, experts say. (2018).

  5. PhRMA. Response to request for comments on negotiating objectives for a U.S.–Japan trade agreement, 83 Fed. Reg. 54,164 (October 26, 2018). (2018).

  6. AARP. 2018 Federal Priorities Letter to OMB. (2018).

  7. United States Office of Management and Budget. Meeting our greatest challenges: opportunity for all. (2017).

  8. Roy, A. A market-based plan for affordable prescription drugs. (2017).

  9. Mestre-Ferrandiz, J., Sussex, J. & Towse A. The R&D cost of a new medicine. (2012).

  10. DiMasi, J.A. & Grabowski, H.G. The cost of biopharmaceutical R&D: is biotech different? MDE Manage. Decis. Econ. 28, 469–479 (2007).

    Article  Google Scholar 

  11. Beall, R.F., Hwang, T.J. & Kesselheim, A.S. Major events in the life course of new drugs, 2000–2016. N. Engl. J. Med. 380, e12 (2019).

  12. United States Food and Drug Administration. CDEr list of licensed biological products with (1) reference product exclusivity and (2) biosimilarity or interchangeability evaluations to date. (2018).

  13. Zhou, S. & Johnson, R. Pharmaceutical probability of success. (2018).

  14. Nocera, J. Drug-price transparency won’t end the patent games. (2018).

  15. United States Food and Drug Administration. New drugs at FDA: CDER’s New Molecular Entities and New Therapeutic Biological Products. (2018).

  16. United States Food and Drug Administration. Drugs@FDA: FDA approved drug products. (2017).

  17. United States Patent and Trade Office. Patent Terms Extended Under 35 USC §156. (2017).

  18. Beall, R.F., Darrow, J.J. & Kesselheim, A.S. Value Health 21, 1382–1389 (2018).

  19. Beall, R.F., Darrow, J.J. & Kesselheim, A.S. Drug Discov. Today 24, 20–25 (2019).

  20. Hemphill, C. S. & Sampat, B. N. J. Health Econ. 31, 327–339 (2012).

    Article  Google Scholar 

  21. Royal Society of Chemistry. The Merck Index Online (2018).

  22. European Patent Office. Espacenet Patent Search (2018).

  23. United States Food and Drug Administration. Advancing health through innovation — 2017 new drug therapy approvals. (2017).

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The authors thank the US Patent and Trademark Office for providing access to patent term restoration data. A.S.K.’s work is supported by Arnold Ventures, the Harvard–MIT Center for Regulatory Science, and the Engelberg Foundation.

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Correspondence to Reed F. Beall.

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Editor’s note: This article has been peer-reviewed.

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Small- vs. large-molecule development times

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Beall, R.F., Hwang, T.J. & Kesselheim, A.S. Pre-market development times for biologic versus small-molecule drugs. Nat Biotechnol 37, 708–711 (2019).

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