Organizations around the world are observing February 28, 2010, as the third annual World Rare Disease Day—an important time for bringing attention to the needs of people
with rare diseases.
The Food and Drug Administration (FDA) is committed to advancing rare disease therapies through the development of orphan products. When former President Ronald Reagan signed the Orphan Drug Act (ODA) of 1983 into law, no one could have imagined then that it would become one of the most important pieces of health care legislation today.
The ODA means hope for more than 25 million Americans who currently have one of 7,000 rare diseases, which includes rare disorders or conditions. More than 350 orphan products for treatment of rare diseases have been approved by FDA since this groundbreaking legislation went into effect. In the decade before the ODA was passed, only 10 treatments had been developed for rare diseases.
What Is an Orphan Drug?
The term "orphan drug" refers to a drug or biologic (such as a vaccine or blood product) that treats a rare disease or condition. The ODA defines a disease as rare if fewer than 200,000 people in the United States have it.
An orphan drug may be a completely new product or an approved drug that's being used in the new context of a rare disease. A drug or biologic must be designated an "orphan drug" through an FDA approval process. To date, more than 2,100 drugs and biologics have been designated as orphan drugs, with more than 350 achieving marketing approval.
What Is a Humanitarian Use Device?
Although medical devices are not eligible for orphan designation, FDA has made it easier and less costly for manufacturers to bring devices for rare diseases to the market through a two-step process.
The first step is FDA approval of the device as a Humanitarian Use Device. The second step is FDA approval to market the device under the Humanitarian Device Exemption (HDE) provisions of the Safe Medical Devices Act of 1990.
This Act allows a medical device to be approved under certain conditions if manufacturers show that the probable benefit outweighs the risks for patients with an extremely rare condition that affects fewer than 4,000 persons in the United States per year. The provision requires only evidence that the probable health benefit of the device is greater than the risk of use—a standard that is less costly to achieve than the level of
safety and effectiveness required for other marketing approvals.
To date, FDA's Office of Orphan Products Development (OOPD) has designated 149 humanitarian use devices, and 50 of those were approved as HDEs. Two such devices
include a stent to treat urinary tract obstruction in unborn babies, and a titanium rib for children born unable to survive without an adequate ribcage. Neither of these devices would have been available outside this program.
How the Orphan Drug Act Has Helped
Developing a new drug or device can be expensive. Because rare diseases affect a relatively small number of people, drug companies generally demonstrate little interest in performing research or development of new products to treat such diseases. Developers face a further difficulty in testing potential treatments because it is difficult to recruit a sufficient number of people to study safety and effectiveness.
The ODA offers a drug developer financial benefits and incentives in exchange for performing research and development, and fulfilling the requirements to get a drug approved for a rare disease or condition.
These financial benefits and incentives include:
? Annual grant funding to defray the cost of clinical testing
? Tax credits for the costs of clinical research
? Assistance in clinical research study designs
? Seven-year period of exclusive marketing after an orphan drug is approved
? Waiver of Prescription Drug User Fee Act (PDUFA) filing fees (over $1,000,000
per application for FY 2010)
These benefits help manufacturers recover the costs of developing a drug for small numbers of people. Since being signed in 1983, the Act has been amended by Congress several times—1984, 1985, 1988, 2007 —to provide further incentives for treatment
In separate legislation in 2007, a newly authorized "priority review voucher" (PRV) for tropical disease treatments may potentially provide additional revenue to support research and development for diseases that are rare in the United States.
FDA's Office of Orphan Products Development
In 1982, FDA established the Office of Orphan Products Development (OOPD) to
identify potential orphan products and to promote the development of those that
demonstrate promise for diagnosing or treating rare diseases.
The office's director, Timothy Coté, M.D., MPH, encourages OOPD to foster the
development of safe and effective treatments for rare diseases by collaborating with:
? medical and research communities
? professional organizations
? pharmaceutical industry
? patient organizations
OOPD's activities during the 2010 calendar year include the following:
? In February, more than 1,000 attendees participated in "The Science of Small
Clinical Trials," which is the second year that OOPD has conducted this training
course in collaboration with NIH's Office of Rare Disease Research. The course
was designed to increase awareness about the special requirements of performing
drug research and evaluation in small populations.
? In 2010, OOPD will be increasing its efforts at searching for abandoned but
promising orphan designated products whose clinical developments are currently
incomplete for a marketing approval. In addition, OOPD will be looking for new
potential orphan products among those products approved for another orphan/
non-orphan indication. The purpose is to make them known to potential orphan
product developers who will hopefully help such products to the “finish line”.
? In 2010, the OOPD launched its orphan drug workshop series, “DO A
DESIGNATION”, which is an opportunity for academic institutions,
biotechnology companies and larger pharmaceutical firms to spend two days
developing applications for orphan status designations. OOPD will provide them
with assistance to find regulatory paths forward for their products. The dates and
locations of the workshops, which are hosted by these co-sponsoring
*February 25-26, 2010; Keck Graduate Institute, Claremont, CA.
*August 3-4, 2010; Center for Orphan Drug Research, College of
Pharmacy, University of Minnesota, Minneapolis, MN.
? In 2010, at the direction of Congress, OOPD will establish within the FDA “a
review group which shall recommend to the Commissioner of Food and Drugs
appropriate preclinical, trial design, and regulatory paradigms and optimal
solutions for the prevention, diagnosis, and treatment of rare diseases.” The
review group has one year to prepare a report with findings and recommendations.
The statutory language is in Agriculture, Rural Development, Food and Drug
Administration, and Related Agencies Appropriations Act of 2010 (H.R. 2997).
Toward a More Promising Future
The ODA promises to identify and address even more challenging opportunities that
might ultimately translate into hope for people with rare diseases or conditions.
According to Dr. Coté , that means continuing and expanding one of the federal
government's most successful grant programs and increasing the number of promising
compounds receiving orphan status designation for rare diseases.
"The good news," Dr. Coté says, "is that dramatic scientific innovations are offering new
hope for the formerly incurable; we are truly on the cusp of a radical transformation in
treatments for rare diseases."
For More Information
Rare Disease Day 2009
FDA Office of Orphan Products Development (OOPD) www.fda.gov/orphan/
NIH Office of Rare Diseases (ORD)
The Genetic and Rare Diseases Information Center http://rarediseases.info.nih.gov/
National Organization for Rare Diseases (NORD) http://www.rarediseases.org/