Orphan Drug Development—International Program and Study Design Issues


The incentives established by the United States Orphan Drug Act in 1983 initiated significant changes within the pharmaceutical industry regarding resources expended to develop products to treat diseases and conditions lacking commercial markets. America’s solution to the orphan drug problem has had worldwide impact and has contributed to an orphan drug law in Japan, proposed legislation in the European Union, and the initiation of a process whereby most Food and Drug Administration-approved orphan drugs and biological products will be similarly approved in Australia.

The international research community faces unique concerns regarding trial design required to obtain approval of products to treat rare diseases. Although safety and efficacy for orphan products cannot be compromised, certain factors impact the research approach and present obstacles to investigators: the life-threatening nature of many orphan diseases; the fact that no other treatment may be available for patients other than the study drug; and the limited number of patients available for clinical trials. Expanding international support for rare disease research is providing stimulus and motivation to overcome these barriers and to encourage development of treatment for very rare diseases. NOTE: The term drug will be used here to specify drug and/or biological product.

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


  1. 1.

    U.S. Federal Food, Drug, and Cosmetic Act (FFDCA). 21 USCA, § 201, et seq.

  2. 2.

    FFDCA SEC. 505(d); 21 USCA § 355(d) (Safety and effectiveness requirements).

  3. 3.

    P.L. 97–414, January 4, 1983 (The Orphan Drug Act).

  4. 4.

    FFDCA, SEC. 525; 21 USCA § 360aa (Recommendations for Investigations of drugs for rare diseases).

  5. 5.

    Section 1.28-1, Title 26, CFR (IRS Regulations on Rare disease research tax credit).

  6. 6.

    Orphan Drug Act Section 5 [21 USCA § 360ee] (Orphan Grant Funding Provision).

  7. 7.

    Draft guidance document; docket number 97D-0100; released for comment March 13, 1997.

  8. 8.

    21CFR Part 316; Orphan Drug Regulations: Final Rule; Federal Register. December 29, 1992.

Download references

Author information



Corresponding author

Correspondence to Marlene E. Haffner MD, MPH.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Haffner, M.E. Orphan Drug Development—International Program and Study Design Issues. Ther Innov Regul Sci 32, 93–99 (1998). https://doi.org/10.1177/009286159803200113

Download citation

Key Words

  • Orphan Drug Act
  • Rare diseases
  • Clinical trials
  • Trial design