Orphan Drugs

The term "orphan drug" as defined by the Orphan Drug Act, refers to a product that treats a rare disease affecting fewer than 200,000 Americans. Or, effects more than 200,000 in the United States with no reasonable expectation that the cost of developing and making available a drug for such disease or condition will be recovered from sales in the United States The Orphan Drug Act was signed into law on January 4, 1983. Since the Orphan Drug Act passed, over 100 orphan drugs and biological products have been brought to market.

The intent of the Orphan Drug Act is to stimulate the research, development, and approval of products that treat rare diseases. This mission is accomplished through several mechanisms:

• Sponsors are granted seven years of marketing exclusivity after approval of its orphan drug product as opposed to the usual three years exclusivity awarded to a non-orphan drug.
• Sponsors also are granted 50% tax credits for clinical trial expenses
• FDA's Office of Orphan Products Development coordinates research study design assistance for sponsors of drugs for rare diseases
• The Office of Orphan Products Development also encourages sponsors to conduct open protocols, allowing patients to be added to ongoing studies.
• Grant funding is available to partially fund Phase I and Phase II clinical trials (http://www.fda.gov/orphan/grants/Instruction2009.html)
• No PDUFA user fees
• Incentives are transferable

Some of the most successful biopharmaceuticals have received the orphan drug designation including Epogen, which was the second highest selling biopharmaceutical in the U.S. with sales of $2,489.0 million in 2007. Other top selling biopharmaceuticals that have been granted orphan drug designation include Enbrel, Avonex, Humira, and Rituxan.[1]

Office of Orphan Products Development

http://www.fda.gov/orphan/

The Food and Drug Administration has charged The Office of Orphan Products Development (OOPD) to dedicate its mission to promoting the development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In fulfilling that task, OOPD interacts with the medical and research communities, professional organizations, academia, governmental agencies, and the pharmaceutical industry, as well as rare disease groups.

The Office of Orphan Products Development (OOPD) administers the major provisions of the Orphan Drug Act (ODA), which provide incentives for sponsors to develop products for rare diseases. Charged by the Food and Drug Administration, the OOPD dedicates its mission to promoting the development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In order to fulfill that task, the OOPD interacts with a variety of players including: the medical and research communities, professional organizations, academia, governmental agencies, and the pharmaceutical industry, as well as rare disease groups. In addition, the OOPD administers the Orphan Products Grants Program, which provides funding for clinical research in rare diseases.

Gaining Orphan Product Designation

A sponsor that submits a request for orphan drug designation of a drug for a specified rare disease or condition shall submit two copies of a completed, dated, and signed request for designation that contains the following:

1. A statement that the sponsor requests orphan drug designation for a rare disease or condition, which shall be identified with specificity.
2. The name and address of the sponsor; the name of the sponsor's primary contact person and/or resident agent including title, address, and telephone number; the generic and trade name, if any, of the drug or drug product; and the name and address of the source of the drug if it is not manufactured by the sponsor.
3. A description of the rare disease or condition for which the drug is being or will be investigated, the proposed indication or indications for use of the drug, and the reasons why such therapy is needed.
4. A description of the drug and a discussion of the scientific rationale for the use of the drug for the rare disease or condition, including all data from nonclinical laboratory studies, clinical investigations, and other relevant data that are available to the sponsor, whether positive, negative, or inconclusive. Copies of pertinent unpublished and published papers are also required.
5. Where the sponsor of a drug that is otherwise the same drug as an already approved orphan 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.
6. Where a drug is under development for only a subset of persons with a particular disease or condition, a demonstration that the subset is medically plausible.
7. A summary of the regulatory status and marketing history of the drug in the United States and in foreign countries, e.g., IND and marketing application status and dispositions, what uses are under investigation and in what countries; for what indication is the drug approved in foreign countries; what adverse regulatory actions have been taken against the drug in any country.
8. Documentation, with appended authoritative references, to demonstrate that: The disease or condition for which the drug is intended affects fewer than 200,000 people in the United States or,
   1. if the drug is a vaccine, diagnostic drug, or preventive drug, the persons to whom the drug will be administered in the United States are fewer than 200,000 per year as specified in § 316.21(b), or
   2. 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).
9. A statement as to whether the sponsor submitting the request is the real party in interest of the development and the intended or actual production and sales of the product.

Tips from the OOPD for Applying for Orphan Product Designation can be found at:
http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/TipsforApplyingforOrphanProductDesignation/default.htm

Research by Eliza Brannigan