How to Get an FDA Orphan Drug Designation

The Orphan Drug Act provides incentives to sponsors to promote the development of drugs for the prevention, diagnoses, and treatment of rare diseases or conditions that affect fewer than 200,000 individuals in the United States, and for which the sponsor is not expected to recover the cost of developing the drug within 7 years post-FDA approval.[1]

History of the Orphan Drug Act

Abbey Meyers, the primary American consumer advocate who pioneered the passage of the 1983 Orphan Drug Act, and then housewife from Connecticut, was the mother of a child with Tourette Syndrome, a rare neurological disorder.

Unfortunately, a clinical study that had previously made a successful treatment available to her son had stopped, as the drug had proven inefficacious for the originally intended and more prevalent target disease. Because it was not commercially viable to continue making the drug for the small market that Abbey Myers’ son represented, the pharmaceutical company stopped making the drug available. A treatment was no longer available for her son’s rare condition.[2]

As a result of robust outreach efforts, combined with a frustrated mother’s will and determination, Abbey Meyers found then California representative, Henry Waxman; together, in 1983, they advocated for the establishment of the Orphan Drug Act. This idea gained traction and, in 1999, the European Medical Agency followed the FDA by passing their own orphan drug law.

Prior to the establishment of the Orphan Drug Act, pharmaceutical companies were not interested in developing drugs for rare diseases because these conditions occurred so infrequently that there was no reasonable expectation that the cost of research, development, and marketing would be recovered. Essentially, there was no “business” in rare disease.

Since the enactment of the Orphan Drug Act, 285 approved orphan drugs are now on the market and an additional 1,400 investigational drugs remain in the pipeline.[3] According to Peter Saltonstall, President and CEO of the National Organization for Rare Disorders (NORD), “More than 9 out of 10 orphan drugs on the market today would never have been developed without the Orphan Drug Act.”[4]

It is often asked whether the Orphan Drug Act made it easier for drugs to be approved. The answer to this question is no; in fact, the efficacy standards for orphan drugs remained the same. The Act simply altered the economics for developing drugs for rare diseases.

Benefits of the Orphan Drug Act

When Should I Request an Orphan Designation?

As soon as prevalence and scientific rationale criteria are met!

If the sponsor has supporting nonclinical and/or clinical efficacy data to support the scientific rationale for their drug product for the prevention, diagnosis, or treatment of a rare disease or condition, and the prevalence of the rare disease is less than 200,000, then the orphan drug designation request may be submitted to the OOPD at any point during drug development, prior to marketing application submission.

To capitalize on the incentives and benefits of the Orphan Drug Act, particularly the tax credits for qualified clinical trial expenditures, sponsors should request orphan drug designation as early as possible during preclinical development.

Key Components of Orphan Drug Designation Requests

  • Description of the rare disease or indication for which the designation is being requested (disease definition, etiology, clinical presentation, signs and symptoms, diagnostic methodologies, and current therapies)
  • Description of limitations in current therapies and unmet needs in the treatment
  • Brief description of the drug (active moiety/principal molecular structure and mechanism of action in the disease)
  • Scientific rationale
  • Indication of applicable disease subsets of nonrare diseases and clinical superiority to previously approved same drugs
  • Prevalence estimate

OOPD Designation Review Process

Per the FDA’s 2017 Orphan Drug Modernization Plan, sponsors may expect to receive OOPD responses to designation requests within 90 days of submission.

Sponsors may obtain 1 of 3 responses to their request:

  • Designation letter
  • Deficiency letter
  • Denial letter

All designations are posted on the Orphan Drug Designations and Approvals public website. If a deficiency letter is received, sponsors have 1 year within which to address the deficiencies and submit a response to the OOPD. Sponsors who have been granted a designation also have the option to withdraw.

Post-Designation Activities

To maintain compliance with the law, orphan drug annual reports are to be submitted within 14 months post‑designation and every 12 months thereafter.

Annual reports are brief progress reports summarizing:

  • Regulatory updates
  • Completed, ongoing, and planned studies
  • Development plans for the upcoming year
  • Changes that may affect orphan drug status

Annual reports are to be submitted via email to the OOPD until marketing authorization is granted, or until the designation is withdrawn.

Sponsors are also required to notify the OOPD within 30 days after the market authorization for the orphan drug’s intended use is submitted to the FDA Review Division, and to notify the OOPD once marketing approval has been granted, so that eligibility for 7‑year market exclusivity may be assessed.

By: Christine Clarke, PhD, Senior Global Regulatory Affairs Manager

Email to get access to our Orphan Drug Submissions checklist, with everything you need to include in your submission and where to submit it.


[1] 21 CFR §316 Orphan Drugs – Code of Federal Regulations (

[2] The Center for Rare and Neglected Diseases at the University of Notre Dame

[3] Drugs For Rare Diseases (

[4] New Study Investigates the Number of Available Orphan Products, Generics and Biosimilars – NORD (National Organization for Rare Disorders) (


Back to MMS Blog