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

Nature Biotechnology volume 37, pages 708–711 (2019)Cite this article

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To the Editor — Before approval by the US Food and Drug Administration (FDA), prescription drugs must be adequately tested in preclinical studies and clinical trials for safety and efficacy. To allow manufacturers sufficient time to earn a profit on resources invested in conducting these studies, brand-name drugs are protected by patents, which last 20 years from the date of application1. The key patents protecting a drug—such as those associated with the drug’s active ingredient—tend to be filed shortly after the new drug is discovered or synthesized. Thus, longer periods of drug development leading up to FDA approval result in reduced time remaining on this fundamental patent during the post-approval period before market entry by competitors2.

Biologic drugs—complex drugs derived from living cells—are thought to be particularly time- and resource-intensive to develop3. The lengthy development process attributed to biologic drugs was cited by legislators when the US Congress passed the Biologics Price Competition and Innovation (BPCIA) in 2009, which granted new biologics 12 years of guaranteed exclusivity. Similarly, the recently proposed renegotiation of the North American Free Trade Agreement (NAFTA)—known as the United States–Mexico–Canada Agreement (USMCA)—would require Canada and Mexico to provide 10 years of exclusivity protections for biologic products for all new drugs4 (Canada currently provides 8 years); expanded biologic exclusivity protections have been proposed in other trade negotiations, such as with Japan5. However, sales of biologic drugs now account for approximately one-third of prescription drug spending in the US, and high prices for these products have led some policymakers and consumer advocates to consider reforms to the BPCIA3,6,7,8.

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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.

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Acknowledgements

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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Authors and Affiliations

  1. Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Reed F. Beall, Thomas J. Hwang & Aaron S. Kesselheim

  2. Cummings School of Medicine and O’Brien Institute of Public Health, University of Calgary, Calgary, Alberta, Canada

    Reed F. Beall

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  1. Reed F. Beall
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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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Supplementary Information

Supplementary Table 1 and Supplementary Figure 1

Supplementary Data

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). https://doi.org/10.1038/s41587-019-0175-2

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