Orphan Drugs

The term “orphan drug,” as defined by the Orphan Drug Act (ODA) of 1983, refers to a drug that treats a rare disease affecting fewer than 200,000 Americans, or one affecting more than 200,000 people and for which there is “no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will [be] recovered from sales in the United States of such drug.”^[1] Orphan drugs are those that treat rare diseases. Unfortunately, pharmaceutical companies may be hesitant to develop drugs that treat these rare conditions, as the drug may generate relatively small sales in comparison to drugs targeting more prevalent diseases. This can lead to the pharmaceutical company incurring a financial loss. The federal government has supported and passed legislation which provides financial incentives to pharmaceutical companies able and willing to develop drugs for rare diseases and conditions.^[1] Since 1983, the U.S. Food & Drug Administration (FDA) has approved more than 650 therapies for rare diseases and conditions. Since 1990, the FDA has approved 72 medical devices for an orphan indication.^[2]

OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OOPD)

The FDA’s Office of Orphan Products Development (OOPD) is tasked with the evaluation and development of promising products (drugs, biologics, devices, and medical foods) for the treatment of rare diseases and conditions. The OOPD evaluates scientific and clinical data submitted by sponsors, identifying promising products for rare diseases and encouraging the development of those medical products. The organization provides incentives for sponsors to develop products for rare diseases.^[3] Programs supported and managed by the OOPD include the:

Orphan Drug Designation Program: This program provides orphan status to drugs and biologics that are intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect less than 200,000 people in the U.S.—or those that affect more than 200,000 people, but are not expected to recover the cost of developing and marketing the drug.
Humanitarian Use Device (HUD) Program: This program focuses on medical devices designed to diagnose or treat rare conditions (those that manifest in fewer than 8,000 people in the U.S., per year). This program designates those medical devices as eligible for the Humanitarian Device Exemption. The Humanitarian Use Device Program has been the first step for 70 Humanitarian Device Exemption approvals.^[4]
Rare Pediatric Disease Priority Review Voucher Program: Through this program, a sponsor that receives an approval for a drug or biologic targeting a rare pediatric disease may qualify for a voucher for a priority review, as it pertains to a subsequent marketing application for a different product.
Orphan Products Grants Program: This grant program provides funding for the clinical research that tests for the safety and efficacy of drugs, biologics, medical devices, and medical foods for the treatment of rare diseases and conditions.
Pediatric Device Consortia (PDC) Grants Program: This grant program provides funding for the development of non-profit consortia, supporting the development of pediatric medical devices.
Orphan Products Natural History Grants Program: This grant program supports studies to advance medical product development for those products targeting rare diseases. Studies will seek to characterize the natural history of rare diseases and conditions, identify genotypic and phenotypic subpopulations, and/or develop or validate clinical outcome measures, biomarkers, or companion diagnostics.^[5]

GAINING ORPHAN PRODUCT DESIGNATION

In order to receive orphan drug designation, a sponsor must submit two copies of a completed, dated, and signed request for designation that contains the following pieces of information:

A statement that the sponsor requests orphan drug designation for a rare disease or condition, which is specifically identified.
The name and address of the sponsor, the name of the sponsor’s primary contact person and/or the resident agent (including title, address, phone number, and email address), the generic and trade name of the drug (if applicable) or the chemical name (or meaningful descriptive name of the drug), and the name and address of the source of the drug (if it is not manufactured directly by the sponsor).
A description of the rare disease or condition for which the drug is being investigated, the proposed use of the drug, and reasons why this drug is needed.
A description of the drug, including the identity of the active moiety, principal molecular structural features, or physical and chemical properties. There should be a discussion of the rationale to establish a medically plausible basis for the use of the proposed drug for the rare condition—including all relevant data from in vitro lab studies, preclinical efficacy studies (conducted in an animal model for the human disease or condition), and clinical experience with the drug in the rare disease or condition (whether positive, negative, or inconclusive). Animal toxicology studies are typically not relevant to a request for orphan drug designation. Copies of related and relevant papers (both unpublished and published) are required.
Where the sponsor of a drug that is otherwise the same drug as an already approved drug seeks orphan drug designation for the subsequent drug for the same rare disease or condition, an explanation of why the proposed variation may be clinically superior to the first drug.
In cases where a sponsor requests orphan drug designation for a drug intended for only a subset of people with a rare disease or condition, a demonstration is required to show that the remaining people with the rare disease or condition would not be appropriate candidates for the drug.
A summary of the regulatory status and marketing history of the drug in the U.S. and foreign countries is required. This may include IND and marketing application status and dispositions, uses under investigation—and in what countries, the indication for the drug approved in foreign countries, and any adverse regulatory actions taken against the drug in any country.
Documentation demonstrating that: the disease or condition for which the drug is intended affects fewer than 200,000 people in the U.S. or—if the drug is a vaccine, diagnostic drug, or preventative drug—persons to whom the drug will be administered in the U.S. are fewer than 200,000 per year as specified in §316.21(b); for a drug intended for diseases or conditions affecting 200,000 or more people, or for a vaccine, diagnostic drug, or preventive drug to be administered to 200,000 or more persons per year in the United States, there is no reasonable expectation that costs of research and development of the drug for the indication can be recovered by sales of the drug in the United States as specified in §316.21(c).^[6]

DATABASES

The FDA maintains the Orphan Drug Product Designation Database, which enables users to generate a list of orphan drugs.

GUIDANCE DOCUMENTS

The following documents may provide additional guidance to sponsors interested in bringing an orphan drug to market:

CONTACT INFORMATION

Office of Orphan Products Development
US Food & Drug Administration
WO32-5295
10903 New Hampshire Avenue
Silver Spring, MD 20993
Phone: (301) 796-8660
Fax: (301) 847-8621
Email: Orphan@fda.hhs.gov

Updated by Theresa Pipher, November 2020