The Orphan Drug Act at 40: Legislative Triumph and the Challenges of Success

Early View Perspective
Pharmaceutical and Medical Device Policy

Policy Points:

  • The Orphan Drug Act (ODA) was the result of patient advocacy and by many measures has been strikingly successful. However, approximately 95% of the more than 7,000 known rare diseases still have no US Food and Drug Administration–approved treatment.
  • The ODA’s success led to sustained criticism of high drug prices, often for products that have orphan drug indications. Critics misconstrue the ODA’s intent and propose reducing its incentives instead of pursuing policies focused on addressing broader prescription drug price challenges that exist in both the orphan and nonorphan drug market.
  • Patients and their families will continue to defend the purpose and integrity of the ODA and to drive investments into rare disease research and clinical development.

Forty years ago, Congress enacted the Orphan Drug Act of 1983 (ODA), one of the most important and successful US laws to stimulate global life science innovation.1 A striking product of grassroots patient advocacy, the ODA has served as the model not only for orphan drug legal frameworks in the European Union, Japan, and other countries2 but also for subsequent US laws intended to correct other market failures of public health importance, such as the dearth of antimicrobial drug development.2

Orphan drugs are those intended to treat rare diseases or conditions that affect fewer than 200,000 Americans or more than 200,000 patients, or for which “there is no reasonable expectation” that the costs of development are recoverable in the United States.1,4 Before 1983, only 38 drugs to treat rare diseases had been approved by the US Food and Drug Administration (FDA). As of the end of 2022, the FDA has approved 882 different drugs for use in the treatment of 392 rare diseases.5,6 Nevertheless, these achievements pale against the burden of the unmet medical needs of patients with rare diseases. More than 30 million Americans are living with a rare disease—a prevalence comparable with type 2 diabetes—and 95% of the more than 7,000 known rare diseases do not yet have an FDA-approved treatment.6,7


  1. The Orphan Drug Act of 1983, 97–414, 97th Cong (1983).
  2. Orphan Medicinal Products Regulation (EC) No.141/2000 of the EuropeanParliament and of the Council, December 16, 1999. Official Journal L 018, January 22, 2000. Accessed November 16, 2023.
  3. The Generating Antibiotic Incentives Now (GAIN) Act, Public Law 112–144(2012).
  4. Section 526 of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bb(1983).
  5. Orphan drugs in the United States: an examination of patents and orphan drugexclusivity. National Organization for Rare Disorders. March 25, 2021. Accessed November 16, 2023.
  6. Fermaglich LJ, Miller KL. A comprehensive study of the rare diseases and con-ditions targeted by orphan drug designations and approvals over the forty yearsof the Orphan Drug Act. Orphanet J Rare Dis. 2023;18:163.

Saltonstall P, Ross H, Kim PT. The Orphan Drug Act at 40: Legislative Triumph and the Challenges of Success. Milbank Q. 2023;102(1):1214.