Magazine Article | August 30, 2012

How To Successfully Navigate The Orphan Designation Process

Source: Life Science Leader

By Brian Bollwage, JD, vice president, strategic regulatory affairs, Theorem Clinical Research

NIH’s Office of Rare Diseases estimates there are more than 6,000 diseases that meet the FDA’s criteria for orphan conditions. A list of these candidate diseases can be viewed at As of July 2012, the FDA has granted orphan designations for 2,617 products, leaving a large number of research targets yet to be pursued.

The Orphan Designation Process

In order to obtain orphan designation for a disease, a sponsor must submit an orphan designation application to the FDA’s Office of Orphan Products Development (OOPD). The required information is described at 21 CFR 316.20(b). Of the nine elementsrequired, there are two particularly critical items — the scientific rationale (item 4) and a convincing demonstration of population prevalence (item 8). The requirement for demonstrating an appropriate scientific rationale has evolved since the 1980’s, when a mere hypothesis for patient benefit was often considered to be sufficient to qualify. Recently, the FDA has become more demanding regarding the scientific rationale. OOPD now requires data validating the clinical benefit, either via a relevant preclinical model of the disease or with actual clinical data. To qualify as an orphan product in the U.S., the patient population must fall below 200,000.

Market Exclusivity, Tax Credits, And Research Grants

The Act includes two significant rewards, which Congress intended to promote the development of drugs to treat rare disease. Most prominent of these is the grant of seven-year market exclusivity and tax credits for certain clinical testing expenses. Regardless of a product’s patent status, market exclusivity begins on the date the FDA approves a designated orphan drug, assuring the exclusive market for a full seven years. Tax incentives allow up to a 50% credit for certain clinical testing expenses from the date of the orphan designation to the date of FDA approval. A marketing application for a product that has been designated as a drug for a rare disease is typically exempt from the standard prescription drug user fee, which is $1.84 million in FY 2012.

There is other help, too. For example, OOPD administers a grant program that underwrites the costs of clinical trials for drugs intended to treat rare diseases. The FDA subsidizes about 70 programs with grants ranging from $200,000 to $350,000. Typically, OOPD funding grants run for three years. Grant applications are solicited via a Federal Register Request for Applications (RFA), published in August each year.

FDA Protocol Assistance

The Orphan Drug Act provides formal protocol assistance upon sponsor request. Protocol review responsibility rests with the center and division holding responsibility for the relevant therapeutic area, but OOPD personnel act as advocates for the sponsor during the protocol review process.

The approval of an orphan designation request does not alter the standard regulatory requirements or process for obtaining market approval. However, the smaller patient populations involved generally justify reliance on data from smaller clinical trials. As a result, orphan applications are reviewed faster on average — 6 months — than the standard 10-month review time.

The FDA has approved more than 400 orphan drugs in the U.S. In 2011 alone, 10 of the 35 new drugs approved were for orphan diseases. There remain substantial opportunities and significant incentives for development of the more than 5,500 rare conditions yet to be addressed. Orphan drugs are estimated to account for 7% of the world pharmaceutical market. With an estimated global market size totalling 1 trillion dollars in 2012, the potential market for orphan drugs approaches $70 billion worldwide.